Indolyl derivatives as liver-X-receptor (LXR) modulators

ABSTRACT

The invention relates to compounds of formula (I): 
                         
and pharmaceutically acceptable salts and pharmaceutically acceptable esters thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A, m, n and p are defined as in claim  1.  These compounds can be used as pharmaceutical compositions for the treatment of, for example, diabetes.

FIELD OF THE INVENTION

The present invention is concerned with novel indole derivatives of theformula (I):

and pharmaceutically acceptable salts and pharmaceutically acceptableesters thereof.

The compounds of the formula I are useful as liver-X-receptormodulators.

All documents cited or relied upon below are expressly incorporatedherein by reference.

BACKGROUND OF THE INVENTION

Liver-X-Receptors (LXRs) are members of the nuclear hormone receptorsuperfamily. The LXRs are activated by endogenous oxysterols andregulate the transcription of genes controlling multiple metabolicpathways. Two subtypes, LXRalpha and LXRbeta, have been described (Willyet al., Genes Dev. 1995, 9:1033–45; Song et al., Proc Natl Acad Sci USA.1994, 91:10809–13). LXRbeta is ubiquitously expressed, while LXRalpha ispredominantly expressed in cholesterol metabolizing tissues such as theliver, adipose, intestine and macrophage. The LXRs modulate a variety ofphysiological responses including regulation of cholesterol absorption,cholesterol elimination (bile acid synthesis), and transport ofcholesterol from peripheral tissues via plasma lipoproteins to theliver. The LXRs are also involved in glucose metabolism, cholesterolmetabolism in the brain, cell differentiation, and inflammation.

At present, approximately half of all patients with coronary arterydisease have low concentrations of plasma high-density lipoproteincholesterol (HDL-C). The atheroprotective function of HDL was firsthighlighted almost 25 years ago and stimulated exploration of thegenetic and environmental factors that influence HDL-C levels (Miller NE., Lipids 1978,13:914–9). The protective function of HDL derives fromits role in a process termed reverse cholesterol transport. HDL mediatesthe removal of cholesterol from cells in peripheral tissues, includingmacrophage foam cells in the atherosclerotic lesions of the arterialwall. HDL delivers its cholesterol to the liver and sterol-metabolizingorgans for conversion to bile and elimination in feces. Studies haveshown that HDL-C levels are predictive of coronary artery disease riskindependently of low-density lipoprotein cholesterol (LDL-C) levels(Gordon et al., Am J Med. 1977, 62:707–14).

At present, the estimated age-adjusted prevalence among Americans age 20and older who have HDL-C of less than 35 mg/dl is 16% (males) and 5.7%(females). A substantial increase of HDL-C is currently achieved bytreatment with niacin in various formulations. However, the substantialunfavorable side-effects limit the therapeutic potential of thisapproach.

It has been observed that as many as 90% of the 14 million diagnosedtype 2 diabetic patients in the United States are overweight or obese,and a high proportion of type 2 diabetic patients have abnormalconcentrations of lipoproteins. Studies have shown that the prevalenceof total cholesterol>240 mg/dl is 37% in diabetic men and 44% in women.The rates for LDL-C>160 mg/dl are 31% and 44%, and for HDL-C<35 mg/dlare 28% and 11%, in diabetic men and women respectively. Diabetes is adisease in which a patient's ability to control glucose levels in bloodis decreased because of partial impairment in response to the action ofinsulin. Type II diabetes (T2D) is also called non-insulin dependentdiabetes mellitus (NIDDM) and has been shown to afflict 80–90% of alldiabetic patients in developed countries. In T2D, the pancreatic Isletsof Langerhans continue to produce insulin. However, the target organsfor insulin action, mainly muscle, liver and adipose tissue, exhibit aprofound resistance to insulin stimulation. The body continues tocompensate by producing unphysiologically high levels of insulin, whichultimately decreases in the later stages of the disease, due toexhaustion and failure of pancreatic insulin-producing capacity. Thus,T2D is a cardiovascular-metabolic syndrome associated with multipleco-morbidities, including insulin resistance, dyslipidemia,hypertension, endothelial dysfunction and inflammatory atherosclerosis.

The first line of treatment for dyslipidemia and diabetes at presentgenerally involves a low-fat and low-glucose diet, exercise and weightloss. However, compliance can be moderate, and as the diseaseprogresses, treatment of the various metabolic deficiencies becomesnecessary with lipid-modulating agents such as statins and fibrates fordyslipidemia, and hypoglycemic drugs, e.g. sulfonylureas, metformin, orinsulin sensitizers of the thiazolidinedione (TZD) class ofPPARγ-agonists, for insulin resistance. Recent studies provide evidencethat modulators of LXRs would result in compounds with enhancedtherapeutic potential, and as such, modulators of LXRs should improvethe plasma lipid profile, and raise HDL-C levels (Lund et al.,Arterioscler. Thromb. Vasc. Biol. 2003, 23:1169–77). LXRs are also knownto control the efflux of cholesterol from the macrophage foam cell ofthe atherosclerotic lesion, and agonists of LXRs have been shown to beatheroprotective (Joseph and Tontonoz, Curr. Opin. Pharmacol. 2003,3:192–7). Thus, modulators of LXRs would be effective treatments for theatherosclerotic disease which underlies the cardiovascular morbidity andmortality of stroke and heart disease. Recent observations also suggestthat there is an independent LXR mediated effect oninsulin-sensitization in addition to its role in atheroprotection (Caoet al., J Biol Chem. 2003, 278:1131–6). Thus LXR modulators can alsoshow superior therapeutic efficacy on HDL-raising and atheroprotection,with additional effects on diabetes, compared to current therapies.

SUMMARY OF THE INVENTION

The present invention relates to compounds of the formula (I):

The present invention also relates to pharmaceutical compositionscomprising a compound of formula (I) and a pharmaceutically acceptablecarrier and/or adjuvant. Furthermore, the present invention relates tothe use of such compounds as therapeutic active substances as well astheir use for the preparation of medicaments for the treatment orprophylaxis of diseases which are modulated by LXR alpha and/or LXR betaagonists. The invention further relates to processes for the preparationof the compounds of formula (I). In addition, the present inventionrelates to a method for the prophylaxis or therapeutic treatment ofdiseases modulated by LXR alpha and/or LXR beta agonists, such asincreased lipid and cholesterol levels, particularly lowHDL-cholesterol, high LDL-cholesterol, atherosclerotic diseases,diabetes, particularly non-insulin dependent diabetes mellitus,metabolic syndrome, dyslipidemia, Alzheimer's disease, sepsis, andinflammatory diseases such as colitis, pancreatitis,cholestasis/fibrosis of the liver, psoriasis and other inflammatorydiseases of the skin, and diseases that have an inflammatory componentsuch as Alzheimer's disease or impaired/improvable cognitive function,and age-related and inherited (e.g. Stargardt's disease) forms ofmacular degeneration, said method comprising administering a compound offormula (I) to a human being or animal.

DETAILED DESCRIPTION

The novel compounds of the present invention have been found to bind toand selectively activate LXR alpha and LXR beta or coactivate LXR alphaand LXR beta. Consequently, cholesterol absorption is reduced, HDLcholesterol is increased, and inflammatory atherosclerosis is reduced.Since multiple facets of combined dyslipidemia and cholesterolhomeostasis are addressed by LXR modulators, novel compounds of thepresent invention have an enhanced therapeutic potential compared to thecompounds already known in the art. They can therefore be used in thetreatment and prophylaxis of diseases which are modulated by LXR alphaand/or LXR beta agonists. Such diseases include increased lipid andcholesterol levels, particularly low HDL-cholesterol, highLDL-cholesterol, atherosclerotic diseases, diabetes, particularlynon-insulin dependent diabetes mellitus, metabolic syndrome,dyslipidemia, Alzheimer's disease, sepsis, and inflammatory diseasessuch as colitis, pancreatitis, cholestasis/fibrosis of the liver,psoriasis and other inflammatory diseases of the skin, and diseases thathave an inflammatory component such as Alzheimer's disease orimpaired/improvable cognitive function. Moreover, the novel compounds ofthe present invention can be used for treatment and prophylaxis ofage-related and inherited (e.g. Stargardt's disease) forms of maculardegeneration.

In the present description the term “alkyl”, alone or in combination,signifies a straight-chain or branched-chain alkyl group with 1 to 8carbon atoms, preferably a straight or branched-chain alkyl group with 1to 6 carbon atoms and particularly preferred a straight orbranched-chain alkyl group with 1 to 4 carbon atoms. Examples ofstraight-chain and branched C₁–C₈ alkyl groups are methyl, ethyl,propyl, isopropyl, butyl, isobutyl, tert.-butyl, the isomeric pentyls,the isomeric hexyls, the isomeric heptyls and the isomeric octyls,preferably methyl and ethyl and most preferred methyl.

The term “cycloalkyl”, alone or in combination, signifies a cycloalkylring with 3 to 8 carbon atoms and preferably a cycloalkyl ring with 3 to6 carbon atoms. Examples of C₃–C₈ cycloalkyl are cyclopropyl,methyl-cyclopropyl, dimethylcyclopropyl, cyclobutyl, methylcyclobutyl,cyclopentyl, methyl-cyclopentyl, cyclohexyl, methyl-cyclohexyl,dimethylcyclohexyl, cycloheptyl and cyclooctyl, preferably cyclopropyl.

The term “alkoxy”, alone or in combination, signifies a group of theformula alkyl-O— in which the term “alkyl” has the previously givensignificance, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,isobutoxy, sec. butoxy and tert.butoxy, preferably methoxy and ethoxyand most preferred methoxy.

The term “aryl”, alone or in combination, signifies a phenyl or naphthylgroup, preferably a phenyl group which optionally carries one or moresubstituents, preferably one to three, each independently selected fromhalogen, trifluoromethyl, trifluoromethoxy, amino, alkyl, alkoxy,alkylcarbonyl, cyano, carbamoyl, alkoxycarbamoyl, methylendioxy,carboxy, alkoxycarbonyl, aminocarbonyl, alkyaminocarbonyl,dialkylaminocarbonyl, hydroxy, nitro, alkyl-SO₂—, amino-SO₂—, cycloalkyland the like. Preferred is phenyl or naphthyl, particularly phenyloptionally substituted with one to three, preferably one or twosubstituents independently selected from alkyl, trifluoromethyl,halogen, alkoxycarbonyl, aminoalkyl, alkoxy, hydroxyl, carboxy andhydroxyalkyl. Particularly preferred is phenyl.

The term “heterocyclyl”, alone or in combination signifies a saturated,partially unsaturated or aromatic 5- to 10-membered heterocycle whichcontains one or more hetero atoms selected from nitrogen, oxygen andsulphur. If desired, it can be substituted on one or more carbon atomse.g. by halogen, alkyl, alkoxy, oxo etc. and/or on a secondary nitrogenatom (i.e. —NH—) by alkyl, cycloalkyl, aralkoxycarbonyl, alkanoyl,phenyl or phenylalkyl or on a tertiary nitrogen atom (i.e.═N—) by oxido,with halogen, alkyl, cycloalkyl and alkoxy being preferred. Examples ofsuch heterocyclyl groups are pyrrolidinyl, piperidinyl, piperazinyl,morpholinyl, thiomorpholinyl, pyrazoyl, imidazoyl (e.g. imidazol-4-yland 1-benzyloxycarbonyl-imidazol-4-yl), pyrazoyl, pyridyl, pyrazinyl,pyrimidinyl, hexahydro-pyrimidinyl, furyl, thienyl, thiazolyl, oxazolyl,indolyl (e.g. 2-indolyl), quinolyl (e.g. 2-quinolyl, 3-quinolyl and1-oxido-2-quinolyl), isoquinolyl (e.g. 1-isoquinolyl and 3-isoquinolyl),tetrahydroquinolyl (e.g. 1,2,3,4-tetrahydro-2-quinolyl),1,2,3,4-tetrahydroisoquinolyl (e.g.1,2,3,4-tetrahydro-1-oxo-isoquinolyl) and quinoxalinyl. Preferred areoxazolyl, quinolinyl, thiazolyl, benzothiophenyl, pyridinyl,2H-pyrazol-3-yl and isoxazolyl. Particularly preferred are oxazol-2-yland oxazol-4-yl.

The term “heteroaryl”, alone or in combination, signifies aromatic 5- to10-membered heterocycle which comprises one or more, preferably one ortwo, particularly preferred one hetero atom selected from nitrogen,oxygen and sulfur, wherein nitrogen is preferred. It can be substitutedon one or more carbon atoms e.g. by cyano, trifluoromethyl,trifluoromethoxy, alkyl-SO₂—, amino-SO₂—, halogen, alkoxy, hydroxy,amino, cycloalkyl, alkylcarbonyl, aminocarbonyl, nitro, alkyl, and/oralkoxycarbonyl. Examples of heteroaryl cycles are thiophenyl orpyrrolidinyl, wherein thiophenyl and pyrrolidinyl are optionallysubstituted with one to three substituents, preferably one or twoindependently selected from alkyl, halogen, alkoxy, trifluoromethoxy,nitro and trifluoromethyl.

The term “amino”, alone or in combination, signifies a primary,secondary or tertiary amino group bonded via the nitrogen atom, with thesecondary amino group carrying an alkyl or cycloalkyl substituent andthe tertiary amino group carrying two similar or different alkyl orcycloalkyl substituents or the two nitrogen substitutents togetherforming a ring, such as, for example, —NH₂, methylamino, ethylamino,dimethylamino, diethylamino, methyl-ethylamino, pyrrolidin-1-yl orpiperidino etc., preferably primary amino, dimethylamino anddiethylamino and particularly dimethylamino.

The term “halogen” signifies fluorine, chlorine, bromine or iodine andpreferably fluorine, chlorine or bromine.

The term “carbonyl”, alone or in combination signifies the —C(O)— group.

The term “nitro”, alone or in combination signifies the —NO₂ group.

The term “cyano”, alone or in combination signifies the group —CN.

The term “formyl”, alone or in combination signifies the group —CHO.

The term “alkenyl”, alone or in combination signifies a straight-chainor branched-chain hydrocarbon group comprising a carbon carbon doublebond and 2 to 10, preferably 2 to 8 carbon atoms, more preferably 2 to 4carbon atoms. Preferred examples are ethenyl and allyl.

The term “alkynyl”, alone or in combination signifies a straight-chainor branched-chain hydrocarbon group comprising a carbon carbon tripplebond and 2 to 10, preferably 2 to 8 carbon atoms, more preferably 2 to 4carbon atoms. Preferred examples are ethynyl and propynyl.

The term “pharmaceutically acceptable salts” refers to those salts whichretain the biological effectiveness and properties of the free bases orfree acids, which are not biologically or otherwise undesirable. Thesalts are formed with inorganic acids such as hydrochloric acid,hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and thelike, preferably hydrochloric acid, and organic acids such as aceticacid, propionic acid, glycolic acid, pyruvic acid, oxylic acid, maleicacid, malonic acid, succinic acid, fumaric acid, tartaric acid, citricacid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid,ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid,N-acetylcystein and the like. In addition these salts may be preparedform addition of an inorganic base or an organic base to the free acid.Salts derived from an inorganic base include, but are not limited to,the sodium, potassium, lithium, ammonium, calcium, magnesium salts andthe like. Salts derived from organic bases include, but are not limitedto salts of primary, secondary, and tertiary amines, substituted aminesincluding naturally occurring substituted amines, cyclic amines andbasic ion exchange resins, such as isopropylamine, trimethylamine,diethylamine, triethylamine, tripropylamine, ethanolamine, lysine,arginine, N-ethylpiperidine, piperidine, polyamine resins and the like.The compound of formula (I) can also be present in the form ofzwitterions. Particularly preferred pharmaceutically acceptable salts ofcompounds of formula (I) are the hydrochloride salts.

The compounds of formula (I) can also be solvated, e.g. hydrated. Thesolvation can be effected in the course of the manufacturing process orcan take place e.g. as a consequence of hygroscopic properties of aninitially anhydrous compound of formula (I) (hydration). The termpharmaceutically acceptable salts also includes physiologicallyacceptable solvates.

“Pharmaceutically acceptable esters” means that compounds of generalformula (I) may be derivatised at functional groups to providederivatives which are capable of conversion back to the parent compoundsin vivo. Examples of such compounds include physiologically acceptableand metabolically labile ester derivatives, such as methoxymethylesters, methylthiomethyl esters and pivaloyloxymethyl esters.Additionally, any physiologically acceptable equivalents of thecompounds of general formula (I), similar to the metabolically labileesters, which are capable of producing the parent compounds of generalformula (I) in vivo, are within the scope of this invention.

In detail, the present invention is concerned with compounds of formula(I),

wherein

-   R¹ is hydrogen, alkyl, halogen, formyl, hydroxyalkyl or    trifluoromethyl;-   R² is hydrogen, alkyl, alkenyl, alkynyl, cyano or halogen;-   R³ is hydrogen or alkyl;-   R⁴ is hydrogen, alkyl, hydroxy or alkoxy;-   R⁵ and R⁶ are independently selected from hydrogen, alkyl,    arylalkyl, heteroarylalkyl, hydroxyalkyl, alkoxycarbonyl, aryl and    heteroaryl;-   A is aryl or heterocyclyl, wherein aryl and heterocyclyl are    optionally substituted with one to three substituents independently    selected from alkyl, halogen, amino, hydroxyalkyl, aryl, aryloxy,    alkoxy, arylalkyl, arylalkenyl, alkoxycarbonylamino,    aminocarbonyloxy, carboxy, alkoxycarbonyl, alkoxycarbonylalkyl,    aminoalkyl, trifluoromethyl, arylalkylaminocarbonyl,    alkoxycarbonylalkylaminocarbonyl, indolylalkylaminocarbonyl,    morpholinylcarbonyl, aminocarbonyl, aminocarbonylalkyl,    aminocarbonylalkoxy, alkoxycarbonylalkoxy,    pyridinylalkylaminocarbonyl, alkyloxycarbonylalkylaryl,    alkyloxycarbonylalkoxyaryl, carboxyalkylaryl, carboxyalkoxyaryl,    aminocarbonylalkylaryl, aminocarbonylalkoxyaryl, aminocarbonylamino,    aminocarbonyloxy, aminocarbonyloxyaryl, carboxyalkyl, carboxyalkoxy,    cycloalkylaminocarbonyl, morpholinylcarbonyloxyaryl,    morpholinylcarbonylaryl, arylalkoxyaryl, aminocarbonylaryl,    pyrrolidinylcarbonyloxyaryl, pyrrolidinylcarbonylaryl,    piperidinylcarbonylaryl, piperidinylcarbonyloxyaryl,    hydroxyalkylaryl, hydroxy(carboxy)alkylaryl,    hydroxy(alkoxycarbonyl)alkylaryl, hydroxy(aminocarbonyl)alkylaryl    and pyridinyl;-   m is zero, 1, 2 or 3;-   n is zero or 1;-   p is zero, 1, 2 or 3; with the proviso that the sum of m, n and p is    1, 2, 3 or 4;    and, wherein the compound is not    2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;    and, wherein the bond between the carbon atoms C^(a) and C^(b) is a    carbon carbon single or double bond and in case the bond between    C^(a) and C^(b) is a carbon carbon double bond R³ and R⁴ are absent;    and pharmaceutically acceptable salts and pharmaceutically    acceptable esters thereof.

The compounds of formula (I) can contain several asymmetric centers andcan be present in the form of optically pure enantiomers, mixtures ofenantiomers such as, for example, racemates, optically purediastereioisomers, mixtures of diastereoisomers, diastereoisomericracemates or mixtures of diastereoisomeric racemates.

Preferred are the compounds of formula (I) and pharmaceuticallyacceptable salts thereof, particularly the compounds of formula (I).

Preferred compounds of formula (I) are those, wherein:

-   R¹ is hydrogen, alkyl, halogen, formyl, hydroxyalkyl or    trifluoromethyl;-   R² is hydrogen, alkyl, alkenyl, alkynyl, cyano or halogen;-   R³ is hydrogen or alkyl;-   R⁴ is hydrogen, alkyl, hydroxy or alkoxy;-   R⁵ and R⁶ are independently selected from hydrogen, alkyl,    arylalkyl, heteroarylalkyl, hydroxyalkyl, alkoxycarbonyl, aryl and    heteroaryl;-   A is aryl or heterocyclyl, wherein aryl and heterocyclyl are    optionally substituted with one to three substituents independently    selected from alkyl, halogen, amino, hydroxyalkyl, aryl, aryloxy,    alkoxy, arylalkyl, alkoxycarbonylamino, aminocarbonyloxy, carboxy,    alkoxycarbonyl, alkoxycarbonylalkyl, aminoalkyl, trifluoromethyl,    arylalkylaminocarbonyl, alkoxycarbonylalkylaminocarbonyl,    indolylalkylaminocarbonyl, morpholinylcarbonyl, aminocarbonyl,    aminocarbonylalkyl, aminocarbonylalkoxy, alkoxycarbonylalkoxy,    pyridinylalkylaminocarbonyl, alkyloxycarbonylalkylaryl,    alkyloxycarbonylalkoxyaryl, carboxyalkylaryl, carboxyalkoxyaryl,    aminocarbonylalkylaryl, aminocarbonylalkoxyaryl, aminocarbonylamino,    aminocarbonyloxy, aminocarbonyloxyaryl, carboxyalkyl, carboxyalkoxy,    cycloalkylaminocarbonyl, morpholinylcarbonyloxyaryl,    morpholinylcarbonylaryl, arylalkoxyaryl, aminocarbonylaryl,    pyrrolidinylcarbonyloxyaryl, pyrrolidinylcarbonylaryl,    piperidinylcarbonylaryl, piperidinylcarbonyloxyaryl;    hydroxyalkylaryl, hydroxy(carboxy)alkylaryl,    hydroxy(alkoxycarbonyl)alkylaryl, hydroxy(aminocarbonyl)alkylaryl    and pyridinyl;    -   m is zero, 1, 2 or 3;    -   n is zero or 1;    -   p is zero, 1, 2 or 3; with the proviso that the sum of m, n and        p is 1, 2, 3 or 4;        and, wherein the compound is not        2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;        and, wherein the bond between the carbon atoms C^(a) and C^(b)        is a carbon carbon single or double bond and in case the bond        between C^(a) and C^(b) is a carbon carbon double bond R³ and R⁴        are absent;        and pharmaceutically acceptable salts and pharmaceutically        acceptable esters thereof.

Further preferred are compounds according to formula (I), wherein R¹ isalkyl, halogen, formyl or hydroxyalkyl. Also preferred are compounds offormula (I), wherein R¹ is hydrogen, alkyl, halogen, hydroxyalkyl ortrifluoromethyl. Moreover, preferred are compounds of formula (I),wherein R¹ is hydrogen, methyl, chloro, iodo, formyl, hydroxymethyl,hydroxyethyl or hydroxypropyl. Particularly preferred are thosecompounds according to formula (I), wherein R¹ is methyl.

Preferred are compounds of formula (I), wherein R² is hydrogen, alkyl,alkenyl, alkynyl or halogen. Further preferred are the compounds offormula (I), wherein R² is hydrogen, alkyl or halogen. Moreover,preferred are the compounds of formula (I), wherein R² is hydrogen,methyl or halogen. Another preferred aspect of the present invention arecompounds of formula (I), wherein R² is alkyl or halogen. Particularlypreferred are those compounds of formula (I), wherein R² is hydrogen.

Further preferred are compounds of formula (I), wherein R³ is alkyl,particularly methyl. Particularly preferred are those compounds offormula (I), wherein R³ is hydrogen.

Another preferred aspect of the present invention are the compoundsaccording to formula (I), wherein R⁴ is hydrogen or alkyl, particularlymethyl. Particularly preferred are those compounds of formula 1, whereinR⁴ is hydrogen.

Further preferred are the compounds of formula (I), wherein R⁵ and R⁶are independently selected from hydrogen, hydroxyalkyl and aryl. Anotherpreferred aspect of the present invention are the compounds of formula(I), wherein R⁵ and R⁶ are independently selected from hydrogen,hydroxymethyl and phenyl. Particularly preferred are the compounds offormula (I), wherein one of R⁵ and R⁶ is hydrogen and the other one ishydroxyalkyl or aryl. Also preferred are the compounds of formula (I),wherein one of R⁵ and R⁶ is hydrogen and the other one is hydroxymethylor phenyl.

Preferred are compounds of formula (I), wherein m is zero, 1 or 2.Further preferred are the compounds of formula (I), wherein m is 1 or 2.Particularly preferred are the compounds of formula (I), wherein m iszero or 1. Other preferred compounds of formula (I) are those, wherein mis 1, n is zero and p is zero.

Further preferred are the compounds of formula (I), wherein n is 1.Particularly preferred are those compounds of formula (I), wherein n iszero.

Preferred are the compounds of formula (I), wherein p is zero, 1 or 2.Further preferred are those compounds of formula (I), wherein p is zeroor 1. Particularly preferred are those compounds of formula (I), whereinp is 1.

Moreover, preferred are the compounds of formula (I), wherein the bondbetween the carbon atoms C^(a) and C^(b) is a carbon carbon single bond.Those compounds are of formula

wherein R¹, R², R³, R⁴, R⁵, R⁶, A, m, n and p are defined as before.

Particularly preferred are those compounds of formula (Ia), wherein

-   R¹ is hydrogen, alkyl, formyl or hydroxyalkyl and-   R², R³, R⁴, R⁵, R⁶, A, m, n and p are defined as before.

Further particularly preferred are those compounds of formula (Ia),wherein

-   R¹ is hydrogen, alkyl, formyl or hydroxyalkyl;-   R² is hydrogen, alkyl, alkenyl, alkynyl or cyano;-   and R³, R⁴, R⁵, R⁶, A, m, n and p are defined as before.

Further preferred are those compounds of formula (I), wherein the bondbetween the carbon atoms C^(a) and C^(b) is a carbon carbon double bondand R³ and R⁴ are absent. Those compounds are of formula

wherein R¹, R², R³, R⁴, R⁵, R⁶, A, m, n and p are defined as before.

Further preferred are the compounds of formula (I), wherein A is phenyl,oxazolyl, quinolinyl, thiazolyl, naphthalenyl, benzothiophenyl,isoxazolyl, quinolinyl, pyridinyl, 2H-pyrazol-3-yl or isooxazolyl,wherein phenyl, oxazolyl, quinolinyl, thiazolyl, naphthalenyl,benzothiophenyl, isoxazolyl, quinolinyl, pyridinyl, 2H-pyrazol-3-yl andisooxazolyl are optionally substituted with one to three substituentsindependently selected from alkyl, halogen, amino, hydroxyalkyl, aryl,aryloxy, alkoxy, arylalkyl, alkoxycarbonylamino, aminocarbonyloxy,carboxy, alkoxycarbonyl, alkoxycarbonylalkyl, aminoalkyl,trifluoromethyl, arylalkylaminocarbonyl,alkoxycarbonylalkylaminocarbonyl, indolylalkylaminocarbonyl,morpholinylcarbonyl, aminocarbonyl, aminocarbonylalkyl,aminocarbonylalkoxy, alkoxycarbonylalkoxy, pyridinylalkylaminocarbonyl,alkyloxycarbonylalkylaryl, alkyloxycarbonylalkoxyaryl, carboxyalkylaryl,carboxyalkoxyaryl, aminocarbonylalkylaryl, aminocarbonylalkoxyaryl,aminocarbonylamino, aminocarbonyloxy, aminocarbonyloxyaryl,carboxyalkyl, carboxyalkoxy, cycloalkylaminocarbonyl,morpholinylcarbonyloxyaryl, morpholinylcarbonylaryl, arylalkoxyaryl,aminocarbonylaryl, pyrrolidinylcarbonyloxyaryl,pyrrolidinylcarbonylaryl, piperidinylcarbonylaryl andpiperidinylcarbonyloxyaryl.

Particularly preferred are those compounds of formula (I), wherein A isphenyl, oxazol-2-yl or oxazol-4-yl, wherein phenyl, oxazol-2-yl andoxazol-4-yl are optionally substituted with one to three substituentsindependently selected from alkyl, tolyl, ethyl-phenyl,trifluoromethyl-phenyl, fluoro-phenyl, chloro-phenyl,carboxymethoxy-phenyl, aminocarbonylmethoxy-phenyl, carboxy-phenyl,hydroxyl-phenyl, hydroxymethyl-phenyl and aminocarbonyl-phenyl. Furtherparticularly preferred are those compounds of formula (I), wherein A isphenyl.

Other preferred compounds of formula (I) as defind above are those,wherein A is oxazolyl which is substituted with a first substituentwhich is alkyl and a second substituent which is phenyl or pyridinyl,which phenyl is substituted with hydroxyalkyl. Preferably, A is2-[4-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl,2-[3-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl or5-methyl-2-pyridin-3-yl-oxazol-4-ylmethyl.

Examples of preferred compounds of formula (I) are those selected fromthe group consisting of:

-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;-   2-(1-Benzyl-3-chloro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2-{1-[2-(4-Ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol;-   2-(1-Benzyl-3-fluoro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(3-morpholin-4-ylmethyl-benzyl)-1H-indol-5-yl]-propan-2-ol;-   3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoic    acid methyl ester;-   2-[1-(3-Dimethylaminomethyl-benzyl)-2-methyl-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-1H-indol-5-yl]-propan-2-ol;-   2-{1-[2-(3-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2-{1-[2-(4-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-1H-indol-5-yl)-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol;-   2-(1-Benzyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-phenethyl-1H-indol-5-yl)-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;-   2-(1-Benzyl-2,3-dichloro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2-{1-[2-(4-tert-Butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2-{1-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2-(1-Benzyl-2,3-diiodo-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1-Benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indole-2-carbaldehyde;-   2-(1-Biphenyl-3-ylmethyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-1H-indol-5-yl)-propan-2-ol;-   2-(1-Benzyl-3-iodo-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   N-Benzyl-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide;-   4-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoic    acid methyl ester;-   N-Methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-phenethyl-benzamide;-   (Methyl-{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoyl}-amino)-acetic    acid ethyl ester;-   3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoic    acid;-   N-[2-(1H-Indol-3-yl)-ethyl]-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide;-   {3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-morpholin-4-yl-methanone;-   N,N-Dimethyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide;-   N-Methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-(2-pyridin-2-yl-ethyl)-benzamide;-   N-Methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-pyridin-2-ylmethyl-benzamide;-   2-[1-Benzyl-2-(1-hydroxy-ethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1-[1-Benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indol-2-yl]-propan-1-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[-(2-hydroxy-1-phenyl-ethyl)-2-methyl-1H-indol-5-yl]-propan-2-ol;-   2-(1-Benzyl-2-hydroxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   N-Cyclohexyl-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide;-   2-[1-(5-Chloro-benzo    [b]thiophen-3-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;-   2-(2-Chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazole-5-carboxylic-acid    methyl ester;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;-   2-(1-Benzyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2{-1-[2-(4-Ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[1-(3-hydroxymethyl-benzyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;-   3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoic    acid methyl ester;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   2-{1-[2-(3-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;-   [2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-phenyl-acetic    acid methyl ester;-   2-{1-[2-(4-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;-   2-(1-Biphenyl-3-ylmethyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[4-(4-trifluoromethyl-phenoxy)-benzyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   2-{1-[2-(4-tert-Butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2-(1-Benzhydryl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoic    acid;-   4-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoic    acid methyl ester;-   1,1,1,3,3,3-Hexafluoro-2-[1-(2-hydroxy-1-phenyl-ethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;-   2-{-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   2-{1-[2-(2,5-Diphenyl-oxazol-4-yl)-ethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   2-{1-[2-(4-Benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2-(1-Benzyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   2-{1-[2-Ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   (4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid methyl ester;-   (4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-(2-methyl-5-phenyl-oxazol-4-yl)-ethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   N,N-Dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide;-   2-{1-[2-(3-Benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid methyl ester;-   3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid methyl ester;-   3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid;-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid;-   3-{4-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid methyl ester;-   2-{1-[2-(2,5-Diphenyl-oxazol-4-yl)-ethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol;-   2-{1-[2-(4-Benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol;-   Dimethyl-carbamic acid    4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenyl    ester;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethyl]-1H-indol-5-yl}-propan-2-ol;-   2-{1-[2-Ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-1H-indol-5-yl}-propan-2-ol;-   (4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid methyl ester;-   (4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid;-   2-{3-Chloro-1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   Pyrrolidine-1-carboxylic acid    4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenyl    ester;-   Morpholine-4-carboxylic acid    4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenyl    ester;-   2-(2-Chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylic    acid;-   2-{1-[2-(2-Chloro-phenyl)-5-hydroxymethyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   N,N-Dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide;-   2-{1-[2-(3-Benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol;-   Morpholine-4-carboxylic acid    3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenyl    ester;-   Dimethyl-carbamic acid    3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenyl    ester;-   Pyrrolidine-1-carboxylic acid    3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenyl    ester;-   (3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid methyl ester;-   3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid methyl ester;-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid methyl ester;-   3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid;-   N,N-Dimethyl-3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide;-   (3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid;-   N,N-Dimethyl-4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   2-[2,3-Dimethyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;-   2-(2-Chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylic    acid methyl ester;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-naphthalen-2-ylmethyl-1H-indol-5-yl)-propan-2-ol;-   1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-1H-indol-5-yl}-propan-2-ol;    and-   {3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-piperidin-1-yl-methanone.

Examples of particularly preferred compounds of formula (I) are thoseselected from the group consisting of:

-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;-   2-(1-Benzyl-3-chloro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   2-{1-[2-(3-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-phenethyl-1H-indol-5-yl)-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;-   2-{1-[2-(4-Ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   2-{1-[2-(3-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;-   1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;-   (4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid;-   N,N-Dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide;-   3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid;-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid;-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol;-   (4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid;-   N,N-Dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide;-   3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol;-   3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid;-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoic    acid;-   N,N-Dimethyl-3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide;-   (3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetic    acid;-   N,N-Dimethyl-4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide;    and-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol.

Other preferred compounds according to formula (I) as defined above arethose selected from the group consisting of:

-   Trans    1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-styryl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,-   2-[1-(2-Benzyl-5-methyl-oxazol-4-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol,-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,-   4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenol,-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol,-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,-   1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,-   1,1,1,3,3,3-Hexafluoro-2-(1-{2-[4-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,-   1,1,1,3,3,3-Hexafluoro-2-(1-{2-[3-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,-   (2R)    1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,-   (2S)    1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,    and-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-pyridin-3-yl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,    and pharmaceutically acceptable salts and pharmaceutically cceptable    esters thereof.

Other particularly preferred compounds according to formula (I) asdefined above are those selected from the group consisting of:

-   1,1,1,3,3,3-Hexafluoro-2-(1-{2-[4-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,-   1,1,1,3,3,3-Hexafluoro-2-(1-{2-[3-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,    and-   1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-pyridin-3-yl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,    and pharmaceutically acceptable salts and pharmaceutically cceptable    esters thereof.

The preparation of compounds of formula (I) of the present invention maybe carried out in sequential or convergent synthetic routes. Synthesesof the invention are shown in the following schemes. The skills requiredfor carrying out the reaction and purification of the resulting productsare known to those in the art. The substituents and indices used in thefollowing description of the processes have the significance given aboveunless indicated to the contrary.

One method to prepare compounds of formula (Ia), in which R¹ to R⁶, m,n, p and A are as above, is illustrated in scheme 1.

An indoline 1 is converted to the hexafluoroisopropanol 2 by treatmentwith hexafluoroacetone sesquihydrate (step a). In an optional step b, 2is O-protected (PG=protecting group) e.g. by treatment with a silylatingagent such as TESCl in presence of a suitable base such as DBU. Both 2and 3 can be N-alkylated to (Ia) and 4, respectively, by treatment witha compound “LG-(CH₂)_(m)(CR⁵R⁶)_(n)—(CH₂)_(p)-A” (wherein LG is aleaving group such as e.g. Cl, Br, I, MsO, TsO or TfO) in a solvent suchas e.g. DMF at 50–180° C. (step c). Alternatively this N-alkylation maybe carried out by reaction with an oxirane 5 (step d) optionally in thepresence of a Lewis acid such as e.g. lithiumperchlorate or ZnCl₂ (inanalogy to e.g.: Chini et al., J. Org. Chem., 1991, 56(20) 5939–5942;Duran Pachon et al., Tet. Lett., 2003, 44(32) 6025–6027), to givederivatives in which m=0, n=1, and R⁶═CH₂OH. Both 2 and 3 may also beN-alkylated by treatment with ClOC(CH₂)_(m-1)(CR⁵R⁶)_(n)—(CH₂)_(p)-A inpresence of a base or with HOOC(CH₂)_(m-1)(CR⁵R⁶)_(n)—(CH₂)_(p)-A in thepresence e.g. EDCI and HOBT or other typical reagents used for theformation of amides from carboxylic acids and amines (step e). Theresulting amide intermediate is reduced in step f (e.g. with BH₃) to4/Ia. Alternatively, the (CH₂)_(m)(CR⁵R⁶)_(n)—(CH₂)_(p)-A-moiety can beintroduced prior to the introduction of thehexafluoroisopropanolyl-group leading to 6, which upon treatment withhexafluoroacetone sesquihydrate is converted to (Ia). Indolines 4 may bedeprotected to indolines (Ia) (e.g. desilylation in the presence ofTBAF).

As shown in scheme 2 (step a), indolines 4 and (Ia), obtained accordingto scheme 1, in which both R³ and R⁴ are H, can be oxidized to theindole 7 and (Ib), respectively (e.g. by treatment with MnO₂ or DDQ).

For indoles 7 or (Ib), in which either R¹ or R²═H, this substituent maybe converted to Cl, Br, I, or F, e.g. by treatment with 1–1.5equivalents of a halogenating agent such as e.g. NCS, NBS, NIS, orN-fluoropyridinium-trifluoromethanesulfonate, respectively (step b).Indoles (1b) or 7 with both R¹ and R²═H, may be dihalogenated using 2–3equivalents of the halogenating agent (step c). Indoles 7 and Ib withR²═Cl, Br or I may be converted to indoles 7 and Ib with R²═CN (step d)e.g. by Pd(II)-mediated coupling with CuCN (e.g. in analogy toSundermeyer et al., Chemistry an European Journal, 2003, 9 (8),1828–1836, or to indoles 7 and Ib in which R² is alkenyl or alkynyl(step e) e.g. by Heck/Stille or Sonogashira type couplings, respectively(e.g. in analogy to Brown et al., Tet. Lett., 2001, 2 (6), 983–985;Kanekiyo et al., Heterocycles, 2000, 53 (9), 1877–1880). Derivativeswith R²=alkenyl or alkynyl may be hydrogenated in presence of e.g. Pd/Cto the derivatives with R²=alkyl (step f). For R²═H, this substituentmay be converted to a methyl substituent; usually this is done bytreatment with 1–1.5 equivalents of DMF and POCl₃ followed byhydrogenolysis in presence of Pd/C of the resulting aldehyde or of thealcohol obtained by reduction (e.g. with LiAlH₄).

Indoles 7 with R¹═Cl, Br or I may be converted to derivatives withR¹=hydroxyalkyl (e.g. by metal-halogen exchange with e.g. anorganolithium and subsequent treatment with paraformaldehyde, analdehylde CHOalkyl or a dialkylketone), to derivatives with R¹=formyl(e.g. by metal-halogen exchange with e.g. an organolithium andsubsequent treatment with a formylating agent such as e.g. DMF), or toderivatives with R¹=alkyl by treatment with an alkylating agent such ase.g. iodomethane after the metal-halogen exchange. Intermediates withR¹═COOH may be obtained by treating the indole with CO₂ after themetal-halogen exchange. Such carboxylic acids can be converted to theindole with R¹═CF₃ e.g. by treatment with SF₄ gas.

Indoles 7 may be deprotected to indoles (Ib) (e.g. desilylation in thepresence of TBAF).

Another method for the preparation of indoles (Ib) in which R¹, R², m,n, and o and A are defined as in claim I, but particularly suited forthe preparation of indoles (Ib), in which R¹ is hydroxyalkyl, formyl oralkyl, is represented in scheme 3.

5-bromoindole 8 is N-alkylated by deprotonation with a sufficientlystrong base (e.g. NaH) and subsequent treatment with a compound“LG-(CH₂)_(m)(CR⁵R⁶)_(n)—(CH₂)_(p)-A” (wherein LG is a leaving groupsuch as e.g. Cl, Br, I, MsO, TsO or TfO) or an epoxide 5 (see scheme 1)to give 9 (step a). For R¹═COOalkyl, a reduction (e.g. with LiAlH₄) iscarried out (step b) and the resulting alcohol is O-protected in step c(e.g. with TIPS-triflate in the presence of DIPEA). Metal halogenexchange with an alkyllithium or a alkylmagnesiumhalogenide (e.g. nBuLi,tertBuLi, EtMgBr) followed by treatment with hexafluoroacetone gas leadsto the indolyl-hexafluoroisopropanol (Ib) (step d). For (Ib) withR¹═CH₂O-PG deprotection may be carried out in step e according to astandard procedure (e.g. desilylation in presence of TBAF) and theresulting alcohol may be oxidized (e.g. with MnO₂) to the formylindole(step f). In an optional step g the 2-formylindole may be O-protected(e.g. by treatment with TESCl in the presence of DBU). Treatment of the2-formylindole with an alkylmagnesiumhalogenide or an alkyllithium leadsto derivatives with R¹=1-hydroxyalkyl (step h). Deoxygenation e.g. byhydrogenolysis in presence of a catalyst such as Pd/C, or by treatmentwith a reducing agent such as e.g. BH₃Me₂S or Et₃Si—H optionally inpresence of an acid or Lewis acid such as e.g. TFA or BF₃.OEt₂ (e.g. inanalogy to Pearlstein et al., Bioorg. and Med. Chem. Lett., 2003, 13,1829–1835; Mewshaw et al., Bioorg. and Med. Chem. Lett., 2002, 12,307–310; Sakagani et al., Synlett. 1996, 163–164) leads to derivativeswith R¹=alkyl (step i). Alternatively derivatives with R¹=alkyl can beobtained from derivatives with R¹=1-hydroxyalkyl by 1,2-eliminationpromoted e.g. by treatment with a sulfonylating agent such as e.g. Tf₂Oin presence of a base such as e.g. DIPEA and subsequent hydrogenation inpresence of e.g. Pd/C, or from derivatives with R¹═CHO by hydrogenationin presence of e.g. Pd/C or by Wittig-type reaction with a phosphoniumylide alkylHC=PPh₃ (e.g. Maryanoff et al., Chem. Rev., 1989, 89,863–927) and subsequent hydrogenation in presence of e.g. Pd/C.

Indoles 7 and (Ib) for which neither R¹ nor R² is a halogen can beconverted to the corresponding indolines 4 and Ib with R³=R⁴=hydrogene.g. by treatment with a reducing agent as e.g. NaBH₄ , NaCNBH₃ orEt₃SiH most often in the presence of an acid such as e.g. TFA.

As mentioned before, indoles 7 may be deprotected to indoles (Ib) (e.g.desilylation in the presence of TBAF).

Another method to prepare indolines (Ia) in which R¹–R⁶, m, n, p and Aare defined as in claim I but particularly suited to prepare derivativesin which at least one of R¹ and R³ is alkyl, R² is alkyl, alkenyl,alkynyl or cyano and R⁴ is hydroxy or alkoxy, is represented in scheme4:

Treatment of 4-(hexafluoro-2-hydroxyisopropyl)aniline 10 withbromo-acetic acid methyl ester followed by NaOH-mediated hydrolylsis ofthe ester moiety leads to the α-aminoacid 11 (steps a and b), which iscyclized in step c to the indoline-3-one 12 e.g. in the presence of TFAAand triphenylphosphineoxide (e.g. in analogy to Hendrickson et al., J.Org. Chem., 1989, 54, 1144–1149). N-alkylation (step d) to give 13 andO-protection (step e) is carried out as described in scheme 1.Deprotonation of 13 with a sufficiently strong base (e.g. LiHMDS) andtreatment with an alkylating agent such as e.g. an alkyliodide leads toderivatives with R³=alkyl and R¹═H (step f). Such a derivative may againbe deprotonated and again be treated with an alkylating agent to givederivatives in which both R¹ and R³ are alkyl (step g). If after thedeprotonation paraformaldehyde, an aldehyde CHOalkyl or a dialkylketoneis added instead of the alkylating agent, this leads to derivatives inwhich R¹ is hydroxyalkyl (step h). The hydroxy group on theR¹-substituent may optionally be protected (e.g. with TIPSOTf in thepresence of DIPEA). Treatment of derivatives 13 with a reducing agentsuch as e.g. LiAlH₄ leads to compounds in which R⁴ is hydroxy and R² ishydrogen (step i), whereas treatment of 13 with anR²-magnesiumhalogenide or a R²-lithium, wherein R²=alkyl, alkenyl oralkynyl, leads to derivatives in which R⁴ is hydroxy and R² is alkyl,alkenyl or alkynyl, respectively (step j). Derivatives in which R²=cyanoand R⁴=hydroxy are obtained from 13 by treatment with a cyanide salt(e.g. KCN) or trimethylsilylcyanide in the presence of a Lewis acid suchas e.g. Ti (O^(i)Pr)₄, Cu(OTf)₂, Zn(OTf)₂ (e.g. Saravan et al., Tet.Lett. 1998, 39 (22), 3823–3824) and subsequent treatment with aqueousHCl (step k). Deoxygenation of derivatives with R⁴=hydroxy toderivatives with R⁴=hydrogen may be carried out as described for step iof scheme 3. Alternatively R⁴=hydroxy may be converted to R⁴=alkoxy(step m) by base-mediated deprotonation (e.g. with LiHMDS) followed bytreatment with an alkylating agent such as e.g. an alkyliodide.Derivatives for which R⁴=hydroxy and R³=hydrogen can be converted to theindole by 1,2-elimination promoted e.g. by treatment with asulfonylating agent such as e.g. Tf₂O in the presence of a suitable basesuch as e.g. DIPEA (step n).

For indolines 4 with R¹=formyl and R³=hydrogen, R³ may be converted toalkyl by deprotonation with a suitable base (e.g. LiHMDS) and subsequenttreatment with an alkylating agent such as e.g. an alkyliodide. Theformyl group may subsequently be converted to hydroxyalkyl as describedin scheme 3 for indoles 7. Deprotonation (e.g. with LiHMDS) andsubsequent treatment with an alkylating agent can be used to convertindolines 4 with R²=cyano and R⁴═H to indolines 4 with R²=cyanoR⁴=alkyl.

As mentioned before, indolines 4 may be deprotected to indolines (Ia)(e.g. desilylation in the presence of TBAF).

If 4, 7, (Ib) or (Ia) contain a functional group not compatible with oneor several of the transformations of R¹–R⁴ described above, thisfunctional group may be suitably protected prior to thetransformation(s) and deprotected again at a later stage of thesynthesis. Such protections and deprotections are carried out accordingto standard literature procedures (as described e.g. in “ProtectiveGroups in Organic Chemistry” by T. W. Greene and P. G. M. Wutts, 2^(nd)Ed., 1991, Wiley N.Y.) and are commonly known to those of the art (e.g.O-silylation of a hydroxy group with TIPSOTf in presence of DIPEA anddesilylation in the presence of TBAF).

The transformations of R¹–R⁴ described above on 4, 7, (Ib) or (Ia) mayalternatively be carried out on an indole with a suitable N-protectinggroup (such as e.g. trimethylsilylethyl or Boc) instead of the(CH₂)_(m)(CR⁵R⁶)_(n)(CH₂)_(p)A-moiety. The(CH₂)_(m)(CR⁵R⁶)_(n)(CH₂)_(p)A-moiety is introduced according to theprocedures described in scheme 1 or scheme 3—preferably on thederivative with R¹=PG—once the N-protecting group has been removed.Introduction and removal of such N-protecting groups is carried outaccording to standard literature procedures (as described e.g. in“Protective Groups in Organic Chemistry” by T. W. Greene and P. G. M.Wutts, 2^(nd) Ed., 1991, Wiley N.Y.) and are commonly known to those ofthe art (e.g. N-Boc-protection with Boc₂O in prescence of DIPEA andremoval of the Boc-protecting group in presence of TFA).

A large number of compounds “LG-(CH₂)_(m)(CR⁵R⁶)_(n)—(CH₂)_(p)-A” withm, n, p, R⁵, R⁶, A, and LG defined as above are commercially available.If not they may be prepared from a related commercially availablestarting material such as e.g. an alcohol“HO—(CH₂)_(m)(CR⁵R⁶)_(n)—(CH₂)_(p)-A”, or an ester“alkylOOC—(CH₂)_(m-1)(CR⁵R⁶)_(n)—(CH₂)_(p)-A” according to standardliterature procedures commonly known to those of the art. If notcommercially available, halogenides of the structure halogen-(CHR⁵)-A,wherein halogen=Cl or Br, are prepared from (CH₂R⁵)-A e.g. by treatmentwith NCS or NBS, respectively (e.g. Togo et al. Syn. Lett., 2003,702–704). Oxiranes such as 5 may be prepared by treatment of1-bisfunctionalized ethenes CH₂═C(R⁵)—(CH₂)_(p)-A with a commonly usedepoxidizing agent such as mCPBA (e.g. Durley et al., J. Med. Chem.,2002, 45, 18, 3891–3904; Tian et al., Org. Lett., 3, 12, 2001,1929–1932). Many of the halogen-(CH₂)_(m)(CR⁵R⁶)_(n)—(CH₂)_(p)-A forwhich m=1, n, p=0, and A=heteroaryl may be prepared according toliterature procedures (e.g. Binggeli et al. WO200292084 and WO97019311,Bouillot et al. WO2004006922; Morita et al., JP9095482; Cynkowski etal., J. Chem. Soc. Chem. Commun., 1995, 2335–2336; Kodama et al., U.S.Pat. No. 6,472,386; Faul et al., Heterocycles, 2001, 55 (4), 689–704.)

After preparation of 4, (Ia), 7, or (Ib) according to the syntheticdescriptions above, functional groups present in A may optionally befurther derivatized. Examples for typical transformations of suchfunctional groups are summarized below:

Benzyloxy is typically transformed to hydroxy, hydroxy toalkoxycarbonylalkoxy, hydroxy (if attached to aryl or heteroaryl) toaryloxy, hydroxy to arylalkoxy, alkoxycarbonyl to hydroxymethyl,hydroxymethyl to formyl, alkoxycarbonyl to carboxy, carboxy toaminocarbonyl, aminocarbonyl to aminomethyl, amino toalkylcarbonylamino, amino to aminocarbonylamino, amino toalkoxycarbonylamino, wherein the just mentioned functional groups may bepresent alone or form part of a larger functional group. Procedures forthese transformations are found in large number in literature and arecommonly known to those of the art.

Formyl may typically be transformed to 1-hydroxyalkyl, by addition of analkylmagnesium halogenide or an alkyllithium. By Zn(0) mediated additionof an α-bromoacetic acid ester (Reformatsky-reaction), the formyl groupmay be derivatized to a 2-(alkoxycarbonyl)-1-hydroxy ethyl group. If the1-hydroxy(alkoxycarbonyl)ethyl is formed from a formyl group directlyattached to an aryl or a heteroaryl, transformation to thealkoxycarbonylethyl-group may be carried out by deoxygenation, e.g byusing one of the conditions mentioned in step i of scheme 3.Alternatively the transformation to the alkoxycarbonylethyl-group may becarried out by 1,2-elimination (e.g. promoted by treatment with Tf₂O inpresence of a base such as DIPEA) and subsequent hydrogenation of thealkene intermediate. Such an alkene intermediate may also be prepareddirectly starting from the formyl-derivative using Wittig-,Wittig-Horner-, Wadsworth-Emmons-, or Peterson-type olefinations.Procedures for such olefinations are found in large amount in literatureand are commonly known to those of the art.

Cl—, Br— and I— substituents attached to aryl or heteroaryl may beconverted to alkenyl, alkynyl, aryl, heterocyclyl, cyano, amino andcarbonylamino, e.g. by Pd(II)-mediated coupling reactions; furthermoreCl—, Br and I— substituents may be transformed to hydroxyalkyl e.g. bymetal-halogen exchange with e.g. an alkyllithium or aalkylmagnesiumhalogenide and subsequent reaction treatment with analdehyde “CHOalkyl”. A hydroxy group directly attached to an aryl orheteroaryl may be transformed to a TfO-substituent (e.g. by treatmentwith Tf₂O in presence of a base such as e.g. DIPEA). The therebyobtained triflate may—in analogy to the Cl—, Br, and I— substituent—beused e.g. for Pd(II)-promoted coupling reactions leading to thereplacement of the TfO-substituent by alkenyl, alkynyl, aryl,heterocyclyl, cyano, amino and carbonylamino (examples may e.g. be foundin: Olofsson et al. J. Org. Chem., 1998, 65 (15), 5076–5079; Buchwald etal., J. Org. Chem., 2000, 65 (4), 1158–1174; Takagi et al., Chem. Lett.,1989, 11, 1957–58).

Prior to the derivatizations of the functional group on A, sensitivefunctional groups on 4, 7, (Ib) or (Ia) may be suitably protected (e.g.silylation of a hydroxy group) and deprotected again whenever desired.Similarly any of the derivatives 4 and 7 as described above may—wheneverdesired—be deprotected to (Ia) and (Ib), respectively. As mentionedbefore, protections and deprotections are carried out according tostandard procedures (as described e.g. in “Protective Groups in OrganicChemistry” by T. W. Greene and P. G. M. Wutts, 2^(nd) Ed., 1991, WileyN.Y.) commonly known to those of the art.

Indolines 1 and indoles 8, if not commercially available, may beprepared from commercially available indolines (such as e.g.indoline-2-carboxylic acid) indoline-2-ones, indoline-3-ones, indoles,anilines, phenylhydrazines, ketones or other related commerciallyavailable starting materials according to literature procedures (asdescribed e.g. in: Advances in Heterocyclic Chemistry, Monograph Seriesby A. Katritzky (Editor); Comprehensive Heterocyclic Chemistry II, areview of Literature 1982–1995, Monograph Series by A. Katritzky(Editor); Indoles (best synthetic methods) by A. Katritky (Editor),Academic Press, London 1996).

The conversion of a compound of formula (I) into a pharmaceuticallyacceptable salt can be carried out by treatment of such a compound withan inorganic acid, for example a hydrohalic acid, such as, for example,hydrochloric acid or hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid etc., or with an organic acid, such as, for example,acetic acid, citric acid, maleic acid, fumaric acid, tartaric acid,methanesulfonic acid or p-toluenesulfonic acid. The correspondingcarboxylate salts can also be prepared from the compounds of formula (I)by treatment with physiologically compatible bases.

The conversion of compounds of formula (I) into pharmaceuticallyacceptable esters or amides can be carried out e.g. by treatment ofsuited amino or hydroxyl groups present in the molecules with ancarboxylic acid such as acetic acid, with a condensating reagent such asbenzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate(BOP) or N,N-dicylohexylcarbodiimide (DCCI) to produce the carboxylicester or carboxylic amide.

Further preferred is a process for the preparation of compounds offormula (I) as above comprising one of the following reactions

reaction of a compound according to formula (II)

in the presence of a compound according to formula (III)

wherein R¹ to R⁶, A, m, n and p are defined as before and LG is aleaving group such as e.g. Cl, Br, I, MsO, TsO, TfO and, wherein hydroxygroups are optionally protected e.g. by treatment with a silylatingagent such as e.g. TESCl, particularly in the presence of a base such ase.g. DBU (see in particular Scheme 1);

oxidation of a compound according to formula (Ia)

wherein R¹, R², R⁵, R⁶, A, m, n and p are defined as before, R³ and R⁴are hydrogen, and, wherein hydroxy groups are optionally protected e.g.by treatment with a silylating agent such as e.g. TESCl, particularly inthe presence of a base such as e.g. DBU.

Preferred intermediates are:

-   -   5-bromo-1-(benzyl)-2-triisopropylsilanyloxymethyl-1H-indole;    -   2-(1-benzyl-2-triisopropylsilanyloxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;        and    -   2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole.

The compounds of formula (I) and their pharmaceutically acceptable saltsand esters can be used as medicaments (e.g. in the form ofpharmaceutical preparations). The pharmaceutical preparations can beadministered internally, such as orally (e.g. in the form of tablets,coated tablets, dragées, hard and soft gelatin capsules, solutions,emulsions or suspensions), nasally (e.g. in the form of nasal sprays) orrectally (e.g. in the form of suppositories). However, theadministration can also be effected parentally, such as intramuscularlyor intravenously (e.g. in the form of injection solutions). Moreover,administration can be effected topically (e.g. in the form of ointments,creams or oils).

The compounds of formula (I) and their pharmaceutically acceptable saltsand esters can be processed with pharmaceutically inert, inorganic ororganic adjuvants for the production of tablets, coated tablets, dragéesand hard gelatin capsules. Lactose, corn starch or derivatives thereof,talc, stearic acid or its salts etc. can be used, for example, as suchadjuvants for tablets, dragées and hard gelatin capsules.

Suitable adjuvants for soft gelatin capsules, are, for example,vegetable oils, waxes, fats, semi-solid substances and liquid polyols,etc.

Suitable adjuvants for the production of solutions and syrups are, forexample, water, polyols, saccharose, invert sugar, glucose, etc.

Suitable adjuvants for injection solutions are, for example, water,alcohols, polyols, glycerol, vegetable oils, etc.

Suitable adjuvants for suppositories are, for example, natural orhardened oils, waxes, fats, semi-solid or liquid polyols, etc.

Suitable adjuvants for topical preparations are glycerides,semi-synthetic and synthetic glycerides, hydrogenated oils, liquidwaxes, liquid paraffins, liquid fatty alcohols, sterols, polyethyleneglycols and cellulose derivatives.

Moreover, the pharmaceutical preparations can contain preservatives,solubilizers, viscosity-increasing substances, stabilizers, wettingagents, emulsifiers, sweeteners, colorants, flavorants, salts forvarying the osmotic pressure, buffers, masking agents or antioxidants.They can also contain still other therapeutically valuable substances.

In accordance with the invention the compounds of formula (I) and theirpharmaceutically acceptable salts can be used for the prophylaxis andtreatment of increased lipid levels, increased cholesterol levels, lowHDL-cholesterol, high LDL-cholesterol, atherosclerotic diseases,diabetes, non-insulin dependent diabetes mellitus, metabolic syndrome,dyslipidemia, sepsis, inflammatory diseases, skin diseases, colitis,pancreatitis, cholestasis of the liver, fibrosis of the liver, maculardegeneration or Alzheimer's disease. The dosage can vary in wide limitsand will, of course, be fitted to the individual requirements in eachparticular case. In general, in the case of oral administration a dailydosage of about 0.1 mg to 20 mg per kg body weight, preferably about 0.5mg to 4 mg per kg body weight (e.g. about 300 mg per person), dividedinto preferably 1–3 individual doses, which can consist, for example, ofthe same amounts, should be appropriate. It will, however, be clear thatthe upper limit given above can be exceeded when this is shown to beindicated.

The invention is illustrated hereinafter by the examples, which have nolimiting character.

EXAMPLES

Abbreviations:

CH₂Cl₂=dichloromethane, BuLi=n-butyllithium,DBU=1,8-diazabicyclo[5.4.0]undec-7-ene,DDQ=2,3-dichloro-5.6-dicyano-p-benzuoquinone, DIPEA=N-ethyldiisopropylamine, DMF=dimethylformamide,EDCl=N-(3-dimthylaminopropyl)-N′-ethylcarbodiimide hydrochloride,EtOAc=ethylacetate, EtOH=ethanol, Et₂O=diethylether, Et₃N=triethylamine,eq=equivalent, HOBT=1-hydroxybenzotriazole, K₂CO₃=potassium carbonate,LiAlH₄=lithium aluminum hydride, LiOH=lithium hydroxide, MeOH=methanol,NaH=sodium hydride, NH₄Cl=ammonium chloride, NaOH=sodium hydroxide,NaOMe=sodium methoxide, NCS=N-chlorosuccinimide, NIS=N-iodosuccinimide,RT=room temperature, TBAF=tetrabutyl ammonium fluoride,TESCl=chlorotriethylsilane, THF=tetrahydrofuran,TIPSOTf=triisopropylsilyl-trifluoromethanesulfonate.

General Remarks

All reactions were performed under argon.

Example 11,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol

To a solution of 32 mg (0.07 mmol) of1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol(example 47) in 0.5 mL of toluene were added 29 mg (0.33 mmol) of MnO₂powder and the mixture was stirred at 70° C. for 10 hrs. Filtration andevaporation of the solvent gave 33 mg (quantitative) of1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol,grey solid, MS: 483 (MH⁺).

Example 22-(1-benzyl-3-chloro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

To a solution of 100 mg (0.26 mmol) of2-(1-benzyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 80) in 1 mL of acetonitrile were added 25 mg (0.185 mmol) ofNCS. After stirring at RT for 2 hrs, the mixture was poured into amixture of a saturated aqueous solution of NH₄Cl and Et₂O. The phaseswere separated and the aqueous one was extracted with Et₂O. The combinedorganic phases were dried over Na₂SO₄ and evaporated. Columnchromatography on silica gel with n-heptane/CH₂Cl₂ 1:3 yielded 70 mg(65%) of2-(1-benzyl-3-chloro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,white solid, MS: 420 ((M−H⁻), 1Cl).

Example 32-{1-[2-(4-ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-{1-[2-(4-ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 49) was prepared2-{1-[2-(4-ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,dark brown solid, MS: 497 (MH⁺).

Example 41,1,1,3,3,3-hexafluoro-2-{1-[2-(3-trifluormethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 56) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(3-trifluormethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 535 (M−H)⁻.

Example 52-(1-benzyl-3-fluoro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

To a solution of 21 mg (0.054 mmol) of2-(1-benzyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 80) in 1 mL of dichloroethane were added 16 mg (0.065 mmol) of1-fluoropyridinium triflate. After stirring at RT for 72 hrs, themixture was poured into a mixture of a saturated aqueous solution ofNH₄Cl and Et₂O. The phases were separated and the aqueous one wasextracted with Et₂O. The combined organic phases were dried over Na₂SO₄and evaporated. Column chromatography on silica gel with n-heptane/EtOAc4:1 yielded 2.5 mg (11%) of2-(1-benzyl-3-fluoro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,light brown waxy solid. MS: 404 (M−H)⁻.

Example 61,1,1,3,3,3-hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 52) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 485 (M−H)⁻.

Example 71,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(3-morpholin-4-ylmethyl-benzyl)-1H-indol-5-yl]-propan-2-ol

In analogy to example 9, from{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-morpholin-4-yl-methanone(example 33) was prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(3-morpholin-4-ylmethyl-benzyl)-1H-indol-5-yl]-propan-2-ol,light yellow oil, MS: 487 (MH⁺).

Example 83-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid methyl ester

In analogy to example 1, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester (example 51), was prepared3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid methyl ester, light yellow solid, MS: 446 (MH⁺).

Example 92-[1-(3-dimethylaminomethyl-benzyl)-2-methyl-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol

A solution of 7 mg (0.0153 mmol) ofN,N-dimethyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide(example 34) in 0.2 mL of THF was treated with 0.006 mL (0.031 mmol) ofborane dimethylsulfide. The mixture was stirred at 70° C. for 10 hrs,treated with MeOH, and concentrated. Column chromatography on silica gelwith n-heptane/EtOAc 4:1 to 1:1 yielded 5 mg (72%) of2-[1-(3-dimethylaminomethyl-benzyl)-2-methyl-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol,light yellow oil, MS: 445 (MH⁺).

Example 101,1,1,3,3,3-hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 54) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 499 (M−H)⁻.

Example 111,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-1H-indol-5-yl]-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol(example 58) was prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-1H-indol-5-yl]-propan-2-ol,orange solid, MS: 507 (MH⁺).

Example 122-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 53) was prepared2-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,light brown solid, MS: 503 (MH⁺, 1Cl).

Example 132-{1-[2-(4-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-{1-[2-(4-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 62) was prepared2-{1-[2-(4-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,light brown solid, MS: 503 (MH⁺, 1Cl).

Example 141,1,1,3,3,3-hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-1H-indol-5-yl)-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 63) was prepared1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-1H-indol-5-yl)-propan-2-ol,light yellow oil, MS: 439 (MH⁺).

Example 151,1,1,3,3,3-hexafluoro-2-{1-[2-(4-trifluormethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 59) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-trifluormethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 535 (M−H)⁻.

Example 16 2-(1-benzyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

16.1

A solution of 5 g (41.96 mmol) of indoline in DMF was treated with 5.8 g(41.96 mmol) of K₂CO₃ and then at 0° C. dropwise, under intensestirring, with 5.5 mL (46.2 mmol) of benzylbromide. The mixture wasstirred at RT for 10 hrs and then for 2 hrs at 60° C. The resultingthick pulp was distributed between a saturated aqueous solution of NH₄Cland Et₂O. Drying of the combined organic phases over Na₂SO₄ andevaporation of the solvent yielded 6.1 g (69%) of N-benzylindoline MS:210 (MH⁺).

16.2

6.1 g (29.15 mmol) of N-benzyl indoline were treated with 6.75 g (30.7mmol) of hexafluoroacetone sesquihydrate and stirred for one week at RT.Distribution between a saturated aqueous solution of NH₄Cl and Et₂O,drying of the organic phase over Na₂SO₄, evaporation of the solvent andcolumn chromatography on silica gel (n-heptane/EtOAc 5:1) yielded 8.6 g(78%) of2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,pink oil, MS: 376 (MH⁺).

16.3

A solution of 8.5 g (22.51 mmol) of2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-olin 60 mL toluene was treated with 9.8 g (112 mmol) of MnO₂ powder. Themixture was stirred for 10 hrs at RT and 8 hrs at 60° C. Filtration andevaporation of the solvent yielded 8.0 g (95%) of2-(1-benzyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol, yellowsolid, MS: 374 (MH⁺).

Example 171,1,1,3,3,3-hexafluoro-2-(2-methyl-1-phenethyl-1H-indol-5-yl)-propan-2-ol

89 mg (ca. 0.17 mmol) of the crude2-methyl-1-phenethyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indoleobtained (example 55) were dissolved in 1 mL of toluene and treated with92 mg (1.1 mmol) of MnO₂ powder. The mixture was stirred at 80° C. for48 hrs, filtrated and the solvent evaporated. The residue was dissolvedin 1 mL of THF and treated with 0.08 mL of a 1M TBAF solution in THF.Stirring for 30 min, evaporation of the solvent and column chromagraphyon silica gel with n-heptane/EtOAc 3:1 yielded 31 mg (ca. 33%) of1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-phenethyl-1H-indol-5-yl)-propan-2-ol,light brown oil, MS: 400 (M−H)⁻.

Example 181,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol(example 57) was prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol,brownish solid, MS: 469 (MH⁺).

Example 192-(1-benzyl-2,3-dichloro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

A solution of 400 mg (1.07 mmol) of2-(1-benzyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol (example16) in 2 mL CH₂Cl₂ was treated portionwise with 286 mg (2.14 mmol) ofNCS and stirred at RT for 10 hrs. Evaporation of the solvent and columnchromatography on silica gel with n-heptane/EtOAc 3:1 to 1:1 yielded 100mg (21%) of2-(1-benzyl-2,3-dichloro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,light brown oil, MS: 441 (M−H)⁻, 2Cl.

Example 202-{1-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-{1-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 66) was prepared2-{1-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,red foam, MS: 525 (MH⁺).

Example 212-{1-[2-(4-chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-{1-[2-(4-chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 71) was prepared2-{1-[2-(4-chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,yellow solid, MS: 517 ((M−H⁻), 1Cl).

Example 222-(1-benzyl-2,3-diiodo-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 26.2 from2-(1-benzyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol (example16) and NIS and stirring at 100° C. instead of 65° C. was prepared2-(1-benzyl-2,3-diiodo-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,light brown oil, MS: 624 (M−H)⁻.

Example 23benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indole-2-carbaldehyde

To a solution of 1.03 g (2.56 mmol) of2-(1-benzyl-2-hydroxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 41) in 10 mL toluene were added 2.22 g (25.6 mmol) of MnO₂powder. The mixture was stirred at 80° C. overnight. Filtration throughdecalite, evaporation of the solvent and column chromatography on silicagel with n-heptane/EtOAc 3:1 yielded 0.342 g (33%) of1-benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indole-2-carbaldehyde,MS: 400 (M−H)⁻.

Example 242-(1-biphenyl-3-ylmethyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-(1-biphenyl-3-ylmethyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 64) was prepared2-(1-biphenyl-3-ylmethyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,yellow viscous oil, MS: 464 (MH⁺).

Example 251,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-1H-indol-5-yl)-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 60), was prepared1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-1H-indol-5-yl)-propan-2-ol,light brown solid, MS: 438 (MH⁺).

Example 262-(1-benzyl-3-iodo-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

26.1

A solution of 6.72 g (18 mmol)2-(1-benzyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol (example16) in DMF was treated with 4.03 mL (27.0 mmol) of DBU and at 0° C. thendropwise with 4.12 mL (27 mmol) TESCl. The mixture was stirred for 2 hrsat RT and the solvent was evaporated. Column chromatography on silicagelwith n-heptane/EtOAc 6:1 yielded 7.7 g (88%) of1-benzyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-1H-indole,light yellow oil, MS: 489 (MH⁺).

26.2

A solution of 1 g (2.1 mmol) of1-benzyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-1H-indolein 7 mL DMF was treated portionwise at 0° C. with 1.94 g (8.6 mmol) ofNIS and stirred for 2 hrs at 65° C. The mixture was poured into amixture of a saturated aqueous solution of NH₄Cl containing NaS₂O₃ andEt₂O. The phases were separated and the aqueous one was extracted withEt₂O. The combined organic phases were dried over Na₂SO₄ and evaporatedto yield 1.1 g (72%) of1-benzyl-3-iodo-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-1H-indole,of which 50 mg were dissolved in 1 mL of MeOH and treated with 0.2 mL of2M NaOMe in MeOH. After stirring for 30 min at RT, the crude mixture wasdistributed between aqueous HCl and Et₂O. The combined organic phaseswere dried over Na₂SO₄ and evaporated. Column chromatography on silicagel with n-heptane/EtOAc 4:1 yielded 30 mg of2-(1-benzyl-3-iodo-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,light brown solid, MS 498 (M−H)⁻.

Example 27N-benzyl-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide

In analogy to example 34, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) and N-methyl benzylamine was preparedN-benzyl-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide,colorless solid, MS: 535 (MH⁺).

Example 284-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid methyl ester

In analogy to example 1, from4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester (example 69) was prepared4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid methyl ester, light yellow solid, MS: 446 (MH⁺).

Example 29N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-phenethyl-benzamide

In analogy to example 34, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) and N-methyl-2-phenethylamine was preparedN-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-phenethyl-benzamide,colorless solid, MS: 549 (MH⁺).

Example 30(methyl-{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoyl}-amino)-aceticacid ethyl ester

In analogy to example 34, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) and sarcosine ethylester hydrochloride was prepared(methyl-{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoyl}-amino)-aceticacid ethyl ester, colorless solid, MS: 531 (MH⁺).

Example 313-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid

In analogy to example 68, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid methyl ester (example 8) was prepared3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid, red solid, MS: 430 (M−H)⁻.

Example 32N-[2-(1H-indol-3-yl)-ethyl]-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide

In analogy to example 34, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) and [2-(1H-indol-3-yl)-ethyl]-methyl-amine waspreparedN-[2-(1H-indol-3-yl)-ethyl]-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide,colorless solid, MS: 588 (MH⁺).

Example 33{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-morpholin-4-yl-methanone

In analogy to example 34, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) and morpholine was prepared{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-morpholin-4-yl-methanone,colorless solid, MS: 501 (MH⁺).

Example 34N,N-dimethyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide

A solution of 60 mg (0.139 mmol) of3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) in 1 mL of THF was treated with 31 mg (0.417 mmol) ofdimethylamine hydrochloride, 0.09 mL (0.834 mmol) of N-methylmorpholine,3.7 mg (0.028 mmol) of HOBT, and 37 mg (0.195 mmol) of EDCl. The mixturewas stirred for 10 hrs at RT and the solvent evaporated. Columnchromatography on silica gel with n-heptane/EtOAc 4:1 to 1:1 yielded 39mg (60%) ofN,N-dimethyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide,colorless solid, MS: 459 (MH⁺).

Example 35N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-(2-pyridin-2-yl-ethyl)-benzamide

In analogy to example 34, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) and 2-(2-aminoethyl)pyridine was preparedN-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-(2-pyridin-2-yl-ethyl)-benzamide,colorless solid, MS: 550 (MH⁺).

Example 36N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-pyridin-2-ylmethyl-benzamide

In analogy to example 34, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) and methylpyridin-2-ylmethylamine was preparedN-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-pyridin-2-ylmethyl-benzamide,colorless solid, MS: 536 (MH⁺).

Example 372-[1-benzyl-2-(1-hydroxy-ethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol

37.1

To a solution of 0.33 g (0.82 mmol) of1-benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indole-2-carbaldehyde(example 23) in 3 mL of DMF at 0° C. were added 0.15 mL (0.99 mmol) ofDBU, followed by 0.17 mL (0.99 mmol) of TESCl. The mixture was stirredat RT overnight and then poured into a mixture of a saturated aqueoussolution of NH₄Cl and Et₂O. The phases were separated and the aqueousone was extracted with Et₂O. The combined organic phases were dried overNa₂SO₄ and evaporated to yield 0.389 g (92%) of1-benzyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-1H-indole-2-carbaldehyde,MS: 516 (MH⁺).

37.2

To a solution of 0.11 g (0.21 mmol) of1-benzyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-1H-indole-2-carbaldehydein 3 mL of THF were added 0.14 mL (0.42 mmol) of methyl magnesiumbromide dropwise at 0° C. under an argon stream. The mixture was stirredat RT for 1.5 h and poured into a mixture of a saturated aqueoussolution of NH₄Cl and Et₂O. The phases were separated and the aqueousone was extracted with Et₂O. The combined organic phases were dried overNa₂SO₄ and evaporated to yield 0.118 g (quantitative) of crude1-[1-benzyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-1H-indol-2-yl]-ethanol,which was dissolved in 2 mL of THF and treated with 0.43 mL (0.43 mmol)of a 1M TBAF-solution in THF, stirred for one hour and then poured intoa mixture of a saturated aqueous solution of NH₄Cl and Et₂O. The phaseswere separated and the aqueous one was extracted with Et₂O. The combinedorganic phases were dried over Na₂SO₄ and evaporated to yield 0.066 g(74%) of2-[1-benzyl-2-(1-hydroxy-ethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol,yellow solid, MS: 418 (M−H)⁻.

Example 381-[1-benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indol-2-yl]-propan-1-ol

In analogy to example 37.2, from1-benzyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-1H-indole-2-carbaldehydeand ethylmagnesium bromide was prepared1-[1-benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indol-2-yl]-propan-1-ol,orange waxy solid, MS: 432 (MH⁺).

Example 391,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 73) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 525 (M−H)⁻.

Example 401,1,1,3,3,3-hexafluoro-2-[1-(2-hydroxy-1-phenyl-ethyl)-2-methyl-1H-indol-5-yl]-propan-2-ol

A solution of 40 mg (0.094 mmol)1,1,1,3,3,3-hexafluoro-2-[1-(2-hydroxy-1-phenyl-ethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol(example 70) in 1 mL of toluene was treated with 45 mg (0.47 mmol) ofMnO₂. After stirring at 80° C. for 8 hrs, 0.5 mL of dioxane and 22 mg(0.094 mmol) of DDQ were added. The resulting mixture was stirred at RTovernight and poured into a saturated aqueous solution of NH₄Cl andEt₂O. The phases were separated and the aqueous one was extracted withEt₂O. The combined organic phases were dried over Na₂SO₄ and evaporated.Column chromatography on silica gel with n-heptane/EtOAc 2:1 yielded 15mg (38%) of1,1,1,3,3,3-hexafluoro-2-[1-(2-hydroxy-1-phenyl-ethyl)-2-methyl-1H-indol-5-yl]-propan-2-ol,brown oil, MS: 418 (MH⁺).

Example 412-(1-benzyl-2-hydroxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

41.1

To a solution of 5 g (19 mmol) of 5-bromoindol-2-carboxylic acid ethylester in 20 mL of anhydrous DMF was added portionwise 1.06 g (24 mmol)of NaH (55% in oil). The mixture was stirred at RT for 45 minutes,treated dropwise with 2.9 mL (24 mmol) of benzyl bromide and stirred forthree hours. After addition of a saturated aqueous solution of NH₄Cl andEt₂O, the phases were separated and the aqueous one was extracted withEt₂O. The combined organic phases were dried over Na₂SO₄ and evaporatedto yield 6.7g (98%) of crude 5-bromo-1-benzylindole-2-carboxylic acidethyl ester, orange oil, MS: 358 (MH⁺).

41.2

To a solution of 6.7 g (19 mmol) of5-bromo-1-(benzyl)indole-2-carboxylic acid ethyl ester in 25 mL ofanhydrous THF at 0° C. were added portionwise 1.42 g (37 mmol) of LiAlH₄and the resulting mixture was stirred at 0° C. for 2 h. After additionof a saturated aqueous solution of NH₄Cl and Et₂O, the phases wereseparated and the aqueous one was extracted with Et₂O. The combinedorganic phases were dried over Na₂SO₄ and evaporated to yield 5.8 g (ca19 mmol) of [5-bromo-1-(benzyl)-1H-indol-2-yl]-methanol, that wasdissolved in 30 mL of CH₂Cl₂ and treated at 0° C. with 4.75 mL (28 mmol)of DIPEA 7.5 mL (28 mmol) of TIPSOTf. The mixture was stirred at RT for1 h and added to saturated aqueous NH₄Cl and Et₂O. The phases wereseparated and the aqueous one was extracted with Et₂O. The combinedorganic phases were dried over Na₂SO₄ and evaporated to yield 7.3 g(81%) of 5-bromo-1-(benzyl)-2-triisopropylsilanyloxymethyl-1H-indole,off-white solid, MS: 473 (MH⁺).

41.3

To a solution of 0.98 g (2.1 mmol) of1-benzyl-5-bromo-2-triisopropylsilanyloxymethyl-1H-indole in 10 mL ofTHF at -78° C. under argon were added dropwise 1.42 mL (1.1 eq.) of a1.6 M BuLi-solution in THF. The mixture was stirred at RT for 15minutes. The solution was cooled again to -78° C. and hexafluoroacetonewas bubbled into the solution for 1 minute. Stirring was continued for10 minutes before ice cubes were added and the mixture was poured into asaturated aqueous solution of NH₄Cl and Et₂O. The phases were separatedand the aqueous one was extracted with Et₂O. The combined organic phaseswere dried over Na₂SO₄ and evaporated. Column chromatography on silicagel with n-heptane/CH₂Cl₂ 2:1 yielded 707 mg (61%) of2-(1-benzyl-2-triisopropylsilanyloxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol, MS: 558(M−H)⁻.

41.4

To a solution of 0.93 g (1.66 mmol) of2-(1-benzyl-2-triisopropylsilanyloxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-olin 10 mL of THF were added 1.66 mL (1.66 mmol) of a 1 M solution oftetrabutyl ammonium fluoride in THF. The mixture was stirred at RT for 1h and poured into a mixture of a saturated aqueous solution of NH₄Cl andEt₂O. The phases were separated and the aqueous one was extracted withEt₂O. The combined organic phases were dried over Na₂SO₄ and evaporatedto yield 1.0 g (quantitative) of2-(1-benzyl-2-hydroxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,light yellow semisolid, MS: 402 (M−H)⁻.

Example 42N-cyclohexyl-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide

In analogy to example 34, from3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid (example 31) and N-methyl cyclohexylamine was preparedN-cyclohexyl-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide,colorless solid, MS: 527 (MH⁺).

Example 43 2-[1-(5-chloro-benzo[b]thiophen-3-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 5-chloro-3-chloromethyl-benzo [b] thiophene wasprepared 2-[1-(5-chloro-benzo [b]thiophen-3-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol,light brown oil, MS: 478 (M−H)⁻.

Example 441,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 4-chloromethyl-5-methyl-3-phenyl-isoxazole wasprepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,light brown oil, MS: 469 (M−H)⁻.

Example 452-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazole-5-carboxylicacid methyl ester

45.1

4-bromomethyl-2-(2-chloro-phenyl)-oxazole-5-carboxylic acid methyl esterwas prepared from 2-chlorobenzaldehyde and racemic glycine in analogy toprocedures by Cynkowski et al. (J. Chem. Soc. Chem. Commun. 1995,2335–2336), Bouillot et al., (WO2004006922), and Morita et al.(JP09095482).

45.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indoleand 4-bromomethyl-2-(2-chloro-phenyl)-oxazole-5-carboxylic acid methylester was prepared2-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazole-5-carboxylicacid methyl ester, yellow oil, MS: 547 ((M−H⁻), 1Cl).

Example 461,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

46.1

2-(2-methyl-phenyl)-4-chloromethyl-5-methyl-oxazole was prepared from2-methyl-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

46.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 2-(2-methyl-phenyl)-4-chloromethyl-5-methyl-oxazolewas prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

Example 471,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

47.1

4-chloromethyl-2-(3-methyl-phenyl)-5-methyl-oxazole was prepared from3-methyl-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

47.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 4-chloromethyl-2-(3-methyl-phenyl)-5-methyl-oxazolewas prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,green solid, MS: 485 (MH⁺).

Example 482-(1-benzyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

48.1

To a solution of 1 g (7.5 mmol) of 2-methyl-2,3-dihydro-1H-indole inanhydrous DMF were added 1.03 g (7.5 mmol) of K₂CO₃ and then dropwise0.97 mL (8.0 mmol) of benzylbromide. The mixture was stirred at RT for3hrs and then distributed between Et₂O and a saturated aqueous solutionof NH₄Cl. The combined organic phases were dried over Na₂SO₄ andevaporated to yield 1.7 g (quantitative) of crude1-benzyl-2-methyl-2,3-dihydro-1H-indole, light blue oil, MS: 224 (MH⁺).

48.2

To 523 mg (2.34 mmol) of 1-benzyl-2-methyl-2,3-dihydro-1H-indole wereadded 1.28 mL (12 mmol) of hexafluoroacetone sesquihydrate. The mixturewas stirred at 80° C. for 4 hrs and then was distributed between Et₂Oand a saturated aqueous solution of NH₄Cl. The combined organic phaseswere dried over Na₂SO₄ and evaporated. Column chromatography on silicagel with n-heptane/EtOAc 4:1 yielded 311 mg (34%) of2-(1-benzyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,light green oil, MS: 388 (M−H)⁻.

Example 492-{1-[2-(4-ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

49.1

2-(3-ethyl-phenyl)-4-chloromethyl-5-methyl-oxazole was prepared from3-ethyl-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

49.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 2-(3-ethyl-phenyl)-4-chloromethyl-5-methyl-oxazolewas prepared2-{1-[2-(3-ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,orange gum, MS: 499 (MH⁺).

Example 501,1,1,3,3,3-hexafluoro-2-[1-(3-hydroxymethyl-benzyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

A solution of 1.29 g (2.24 mmol) of3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester (example 51) in 5 mL of THF was treated at 0° C. with87 mg (2.24 mmol) of a LiAIH₄. The mixture was stirred for 1 h at RT,treated subsequently with MeOH and H₂O. Distribution between Et₂O and asaturated aqueous solution of NH₄Cl, drying of the combined organicphases over Na₂SO₄ and evaporation, yielded 1.07 g (90%) of{3-[2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-phenyl}-methanol,of which 50 mg were dissolved in 1 mL of THF and treated with 0.14 mL ofa 1M TBAF-solution in THF. After stirring at RT for 2 hrs, the solutiondistributed between Et₂O and saturated aqueous NH₄Cl. The combinedorganic phases were dried over Na₂SO₄ and evaporated, yielding 49 mg(quantitative) of1,1,1,3,3,3-hexafluoro-2-[1-(3-hydroxymethyl-benzyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,yellow gum, MS: 420 (MH⁺).

Example 513-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester

51.1

To 2.5 mL (19.1 mmol) of 2-methyl-2,3-dihydro-1H-indole were added 2.1mL (19.1 mmol) of hexafluoroacetone sesquihydrate dropwise at 0° C.After stirring at 80° C. for 12 hrs, the mixture was distributed betweenEt₂O and a saturated aqueous solution of NH₄Cl. The combined organicphases were dried over Na₂SO₄ and evaporated. Column chromatography onsilica gel with n-heptane/EtOAc 4:1 yielded 1.41 g (25%) of1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol,off-white solid, MS: 300 (MH⁺).

51.2

To a solution of 5.9 g (19.7 mmol) of1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-olin DMF were added 2.94 mL (19.7 mmol) of DBU and after 30 min 3.3 mL(19.7 mmol) of TESCl. After 10 hrs, additional 0.44 mL (3.0 mmol) of DBUand 1.65 mL (9.85 mmol) of TESCl were added and stirring was continuedfor 2 hrs. The solvent and excess TESCl were evaporated i.v. and theresidue was distributed between Et₂O and a saturated aqueous solution ofNH₄Cl. The combined organic phases were dried over Na₂SO₄ and evaporatedto yield 8.1 g (99%) of2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole,red liquid, MS: 414 (MH⁺).

51.3

To a solution of 94 mg (0.23 mmol) of2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indolein 0.5 mL of DMF were added 104 mg (0.45 mmol) of 3-chloromethyl-benzoicacid methyl ester and the mixture was stirred at 80° C. for 10 hrs.After cooling to RT the mixture was treated with 0.5 mL of a 1M solutionof TBAF in THF and stirred for an hour at 60° C. Evaporation of thesolvent and chromatography on silica gel with EtOAc/n-heptane gave 58 mg(99%) of3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester, light red oil, MS: 448 (MH⁺).

Example 521,1,1,3,3,3-hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

52.1

2-(2-fluoro-phenyl)-4-chloromethyl-5-methyl-oxazole was prepared from1-fluoro-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

52.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 2-(2-fluoro-phenyl)-4-chloromethyl-5-methyl-oxazolewas prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light yellow oil, MS: 487 (M−H)⁻.

Example 532-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

53.1

4-chloromethyl-2-(3-chloro-phenyl)-5-methyl-oxazole was prepared from3-chloro-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

53.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 4-chloromethyl-2-(3-chloro-phenyl)-5-methyl-oxazolewas prepared2-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,light yellow solid, MS: 505 (MH⁺), 1Cl.

Example 541,1,1,3,3,3-hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

54.1

2-(4-fluoro-3-methyl-phenyl)-4-chloromethyl-5-methyl-oxazole wasprepared from 4-fluoro-3-methyl-benzaldehyde in analogy to the procedureby Binggeli et al. (WO200292084).

54.2

In analogy to example 51.3 from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and2-(4-fluoro-3-methyl-phenyl)-4-chloromethyl-5-methyl-oxazole wasprepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 501 (M−H)⁻.

Example 551,1,1,3,3,3-hexafluoro-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol

A solution of 101 mg (0.24 mmol) of2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) in CH₂Cl₂ was treated with 0.05 mL (0.3 mmol) of DIPEAand then with 0.03 mL (0.24 mmol) of phenylacetylbromide at 0° C. Themixture was stirred at RT for 3 hrs and then distributed between Et₂O asaturated aqueous solution of NH₄Cl. The combined organic phases weredried over Na₂SO₄ and evaporated to yield 120 mg of1-[2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-2-phenyl-ethanone.This crude was dissolved in 2 mL of THF and treated with 0.9 mL of a 1MBH₃ soution in THF. After stirring for 10 hrs at RT the mixture wasdistributed between Et₂O and a saturated aqueous solution of NH₄Cl. Thecombined organic phases were dried over Na₂SO₄ and evaporated to yield135 mg of2-methyl-1-phenethyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole,of which 30 mg were dissolved in 1 mL of THF and treated with 0.07 mL of1M TBAF in THF. Stirring for 30 min, evaporation, and columnchromatography on silica gel with n-heptane/EtOAc (4:1) yielded 12 mg(51%) of1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol,colorless waxy solid, MS: 404 (MH⁺).

Example 561,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

56.1

2-(3-trifluormethyl-phenyl)-4-chloromethyl-5-methyl-oxazole was preparedfrom 3-trifluoromethyl-benzaldehyde in analogy to the procedure byBinggeli et al. (WO200292084).

56.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and2-(3-trifluormethyl-phenyl)-4-chloromethyl-5-methyl-oxazole was prepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,yellow oil, MS: 537 (M−H)⁻.

Example 571,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

57.1

4-chloromethyl-5-methyl-2-phenyl-oxazole was prepared from benzaldehydein analogy to the procedure by Binggeli et al. (WO200292084).

57.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 4-chloromethyl-5-methyl-2-phenyl-oxazole was prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,yellowish solid, MS: 471 (MH⁺).

Example 581,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 6-chloromethyl-2-trifluoromethyl-quinoline wasprepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,light red oil, MS: 509 (MH⁺).

Example 591,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

59.1

2-(4-trifluormethyl-phenyl)-4-chloromethyl-5-methyl-oxazole was preparedfrom 4-trifluoromethyl-benzaldehyde in analogy to the procedure byBinggeli et al. (WO200292084).

59.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and2-(4-trifluormethyl-phenyl)-4-chloromethyl-5-methyl-oxazole was prepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,yellow semisolid, MS: 537 (M−H)⁻.

Example 601,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 1-chloromethyl-naphthalene was prepared1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol,light brown solid, MS: 440 (MH⁺).

Example 61[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-phenyl-aceticacid methyl ester

A solution of 0.14 g (0.34 mmol)2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) in 1.5 mL of methanol was treated with 0.028 g (0.34mmol) of sodium actetate and 0.053 mL (0.34 mmol) of α-bromophenylmethyl acetate. The mixture was stirred at 100° C. in a pressure tubefor 10 hrs and then distributed between Et₂O and a saturated aqueoussolution of NH₄Cl. The combined organic phases were dried over Na₂SO₄and evaporated. Column chromatography on silica gel with n-heptane/EtOAc4:1 yielded 170 mg of[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-phenyl-aceticacid methyl ester, colourless viscous oil, MS: 448 (MH⁺).

Example 622-{1-[2-(4-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

62.1

4-chloromethyl-2-(4-chloro-phenyl)-5-methyl-oxazole was prepared from4-chloro-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

62.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 4-chloromethyl-2-(4-chloro-phenyl)-5-methyl-oxazolewas prepared2-{1-[2-(4-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,light yellow solid, MS: 505 (MH⁺).

Example 631,1,1,3,3,3-hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 2-chloromethyl-quinoline was prepared1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol,yellow semisolid, MS: 441 (MH⁺).

Example 642-(1-biphenyl-3-ylmethyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 3-chloromethyl-biphenyl was prepared2-(1-biphenyl-3-ylmethyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,brown oil, MS: 466 (MH⁺).

Example 651,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[4-(4-trifluoromethyl-phenoxy)-benzyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

65.1

4-chloromethyl-(4-trifluoromethyl-phenoxy)-benzene was prepared inanalogy to a procedure described for the preparation of4-chloromethyl-phenoxybenzene by Binggeli et al. (WO97019311).

65.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 4-chloromethyl-(4-trifluoromethyl-phenoxy)-benzenewas prepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[4-(4-trifluoromethyl-phenoxy)-benzyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light brown oil, MS: 550 (MH⁺).

Example 662-{1-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

66.1

2-(4-tert-butyl-phenyl)-4-chloromethyl-5-methyl-oxazole was preparedfrom 4-tert-butyl-1-benzaldehyde in analogy to the procedure by Binggeliet al. (WO200292084).

66.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and2-(4-tert-butyl-phenyl)-4-chloromethyl-5-methyl-oxazole was prepared2-{1-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,red solid, MS: 527 (MH⁺).

Example 672-(1-benzhydryl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and diphenylmethylbromide was prepared2-(1-benzhydryl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,yellow oil, MS: 466 (MH⁺).

Example 683-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid

A solution of 66 mg (0.118 mmol) of3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester (example 61) in 0.5 mL of THF was treated with 0.2 mLof a 1M aqueous LiOH solution and stirred for 10 hrs at RT. The solventswere evaporated and the residue distributed between EtOAc and a aqueoussolution of NH₄Cl. Drying of the combined organic phases over Na₂SO₄ andevaporation of the solvent yielded 51 mg (99%) of3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid, light yellow gum, MS: 432 (M−H)⁻.

Example 694-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 4-chloromethyl-benzoic acid methyl ester was prepared4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester, light red oil, MS: 448 (MH⁺).

Example 701,1,1,3,3,3-hexafluoro-2-[1-(2-hydroxy-1-phenyl-ethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

70.1

To a solution of 114 mg (0.275 mmol) of2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) in 1 mL of acetonitrile were added 0.063 mL (0.55 mmol)of racemic phenyloxirane and 58 mg (55 mmol) of lithiumperchlorate.After stirring at 80° C. for 18 hrs, the mixture was distributed betweenEt₂O and a saturated aqueous solution of NH₄Cl. The combined organicphases were dried over Na₂SO₄ and evaporated. Column chromatography onsilica gel with n-heptane/EtOAc 4:1 yielded 77 mg (52%) of2-[2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-2-phenyl-ethanol,MS: 534 (MH⁺).

70.2

To a solution of 19 mg (0.036 mmol) of2-[2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-2-phenyl-ethanolin 0.5 mL THF were added 0.043 mL (0.043 mmol) of a 1M TBAF solution inTHF. After stirring at RT for 24 hrs the mixture was distributed betweenEt₂O and a saturated aqueous solution of NH₄Cl. The combined organicphases were dried over Na₂SO₄ and evaporated. Column chromatography onsilica gel with n-heptane/EtOAc 2:1 yielded 9.3 mg (62%) of1,1,1,3,3,3-hexafluoro-2-[1-(2-hydroxy-1-phenyl-ethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,yellow viscous oil, MS: 420 (MH⁺).

Example 712-{1-[2-(4-chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

71.1

4-chloromethyl-2-(4-chloro-phenyl)-5-methyl-thiazole was preparedaccording to the procedure described by Yamane et al. (Tet. Lett., 45,2004, 69–74 and WO2001019805).

71.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 4-chloromethyl-2-(4-chloro-phenyl)-5-methyl-thiazolewas prepared2-{1-[2-(4-chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,yellow oil, MS: 519 ((M−H⁻), 1Cl).

Example 721,1,1,3,3,3-hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

72.1

4-chloromethyl-(4-fluoro-phenoxy)-benzene was prepared in analogy to aprocedure described for the preparation of 4-chloromethyl-phenoxybenzeneby Binggeli et al. (WO97019311).

72.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and chloromethyl-3-(4-fluoro-phenoxy)-benzene wasprepared1,1,1,3,3,3-hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light red oil, MS: 500 (MH⁺).

Example 731,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

73.1

2-(4-isopropoxy-phenyl)-4-chloromethyl-5-methyl-oxazole was preparedfrom 4-isopropoxy-benzaldehyde in analogy to the procedure by Binggeliet al. (WO200292084).

73.2

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and2-(4-isopropoxy-phenyl)-4-chloromethyl-5-methyl-oxazole was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light yellow oil, MS: 527 (M−H)⁻.

Example 741,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and3-chloromethyl-2-methyl-6-(4-trifluoromethyl-phenyl)-pyridine wasprepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 549 (MH⁺).

Example 752-{1-[2-(2,5-diphenyl-oxazol-4-yl)-ethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

75.1

In analogy to example 85.1, from benzaldehyde and1-phenyl-1,2-propanedione 2-oxime instead of diacetylmonooxyme wasprepared 2-(2,5-diphenyl-oxazol-4-yl)-ethanol. Transformation of2-(2,5-diphenyl-oxazol-4-yl) ethanol to4-(2-bromo-ethyl)-2,5-diphenyl-oxazole was carried out by O-mesylationfollowed by treatment with NaBr, in analogy to the procedure by Faul etal. (Heterocycles, 2001, 55(4) 689–704).

75.2

A solution of 100 mg (0.33 mmol) of1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and 4-(2-bromo-ethyl)-2,5-diphenyl-oxazole in 0.5 mL ofDMF was stirred at 80° C. overnight. Distribution of the mixture betweena saturated aqueous solution of NH₄Cl and Et₂O, drying of the combinedorganic phases over Na₂SO₄ and column chromatography on silica gel withn-heptane/EtOAc 4:1 yielded 39 mg (21%) of2-{1-[2-(2,5-diphenyl-oxazol-4-yl)-ethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,light yellow gum, MS: 547 (MH⁺).

Example 761,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

76.1

4-chloromethyl-2-(4-isopropyl-phenyl)-5-methyl-oxazole was prepared from4-isopropyl-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

76.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and4-chloromethyl-2-(4-isopropyl-phenyl)-5-methyl-oxazole was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,orange oil, MS: 513 (MH⁺).

Example 771,1,1,3,3,3-hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

77.1

4-chloromethyl-2-(2-methoxy-phenyl)-5-methyl-oxazole was prepared from2-methoxy-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

77.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and 4-chloromethyl-2-(2-methoxy-phenyl)-5-methyl-oxazolewas prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light yellow gum, MS: 501 (MH⁺).

Example 781,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

78.1

4-chloromethyl-2-(2-trifluoromethyl-phenyl)-5-methyl-oxazole wasprepared from 2-trifluoromethyl-benzaldehyde in analogy to the procedureby Binggeli et al. (WO200292084).

78.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and4-chloromethyl-2-(2-trifluoromethyl-phenyl)-5-methyl-oxazole wasprepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light yellow gum, MS: 539 (MH⁺).

Example 792-{1-[2-(4-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

79.1

4-chloromethyl-2-(4-benzyloxy-phenyl)-5-methyl-oxazole was prepared from4-benzyloxy-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

79.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and4-chloromethyl-2-(4-benzyloxy-phenyl)-5-methyl-oxazole was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light brown foam, MS: 577 (MH⁺).

Example 802-(1-benzyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol

A solution of 31 mg (0.055 mmol) of2-(1-benzyl-2-triisopropylsilanyloxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 41.3) in 1 mL of methanol was hydrogenated at atmosphericpressure for 12 hours in the presence of 30 mg of Pd/C (10% Pd). Removalof the catalyst by filtration through decalite and evaporation of thesolvent yielded 20 mg (93%) of2-(1-benzyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol,red solid, MS: 388 (MH⁺).

Example 811,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

81.1

5-chloromethyl-1-methyl-3-(4-trifluoromethyl-phenyl)-1H-pyrazole wasprepared in analogy to the preparation of5-chloromethyl-1-methyl-3-(3,4,5-trimethoxy-phenyl)-1H-pyrazoledescribed by Kodama et al. (U.S. Pat. No. 6,472,386), but starting from4-trifluoromethylacetophenone instead of 3′4′5′-trimethoxyacetophenone.

81.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and5-chloromethyl-1-methyl-3-(4-trifluoromethyl-phenyl)-1H-pyrazole wasprepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 538 (MH⁺).

Example 822-{1-[2-ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

82.1

5-chloromethyl-1-ethyl-3-(4-trifluoromethyl-phenyl)-1H-pyrazole wasprepared in analogy to the prepaparation of5-chloromethyl-1-ethyl-3-(3,4,5-trimethoxy-phenyl)-1H-pyrazole describedby Kodama et al. (U.S. Pat. No. 6,472,386), but starting from4-trifluoromethylacetophenone instead of 3′4′5′-trimethoxyacetophenoneand using ethyl hydrazine instead of methylhydrazine.

82.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and5-chloromethyl-1-ethyl-3-(4-trifluoromethyl-phenyl)-1H-pyrazole wasprepared2-{1-[2-ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,yellow oil, MS: 552 (MH⁺).

Example 83(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester

A solution of 40 mg (0.083 mmol) of4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenol(example 99) in 0.5 mL of DMF was treated with 0.01 mL of DBU and 0.01mL (0.1 mmol) of methylbromoacetate. The mixture was stirred overnightat RT and distributed between Et₂O and a saturated aqueous solution ofNH₄Cl. Drying of the combined organic phases, evaporation of the solventand chromatography on silica gel with n-heptane/EtOAc 1:1 gave(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester, off-white foam, MS: 559 (MH⁺).

Example 84(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid

In analogy to example 91, from(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester (example 83) was prepared(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid, light yellow solid, MS: (545, MH⁺).

Example 851,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-(2-methyl-5-phenyl-oxazol-4-yl)-ethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

85.1

2-(5-methyl-2-phenyl-oxazol-4-yl)-ethanol was obtained from benzaldehydeand diacetylmonooxime in analogy to the procedure by Binggeli et al.(WO200292084). Transformation of 2-(2,5-diphenyl-oxazol-4-yl)-ethanol to4-(2-bromo-ethyl)-2,5-diphenyl-oxazole was carried by 0-mesylationfollowed by treatment with NaBr in analogy the procedure by Faul et al.(Heterocycles, 2001, 55(4), 689–704).

85.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and 4-(2-bromo-ethyl)-5-methyl-2-phenyl-oxazole wasprepared1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-(2-methyl-5-phenyl-oxazol-4-yl)-ethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,MS: 485 (MH⁺).

Example 861,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

86.1

5-chloromethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-oxazole wasprepared in analogy to a procedure by Sznaidman et al. (Bioorg. Med.Chem. Letters, 2003, 13(9) 1517-1521 and WO2001000603).

86.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and5-chloromethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-oxazole wasprepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 539 (MH⁺).

Example 87N,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide

In analogy to example 34, from(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid (example 84) and dimethylamine hydrochloride was preparedN,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide,white foam, MS: 572 (MH⁺).

Example 882-{1-[2-(3-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

88.1

4-chloromethyl-2-(3-benzyloxy-phenyl)-5-methyl-oxazole was prepared from3-benzyloxy-benzaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

88.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and2-(3-benzyloxy-phenyl)-4-chloromethyl-5-methyl-oxazole was prepared2-{1-[2-(3-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,orange solid, MS: 577 (MH⁺).

Example 894-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester

89.1

4-(4-chloromethyl-5-methyl-oxazol-2-yl)-benzoic acid methyl ester wasprepared from 3-formyl-benzoic acid methyl ester in analogy to theprocedure by Binggeli et al. (WO200292084).

89.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and 4-(4-chloromethyl-5-methyl-oxazol-2-yl)-benzoic acidmethyl ester was prepared4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester, yellow gum, MS: 529 (MH⁺).

Example 903-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester

90.1

4-(4-chloromethyl-5-methyl-oxazol-2-yl)-benzoic acid methyl ester wasprepared from 3-formyl-benzoic acid methyl ester in analogy to theprocedure by Binggeli et al. (WO200292084).

90.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and 3-(4-chloromethyl-5-methyl-oxazol-2-yl)-benzoic acidmethyl ester was prepared3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester, off-white solid, MS: 529 (MH⁺).

Example 913-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid

A solution of 50 mg (0.095 mmol) of3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 90) was added 1 mL of a 1M aqueousLiOH-solution and the mixture stirred at RT for 1 h. After acidificationwith aqueous HCl to pH of ca 3–4, Et₂O was added, the phases wereseparated and the aqueous one extracted with Et₂O. The combined organicphases were dried over Na₂SO₄ and evaporated to yield 49 mg(quantitative) of3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid, off-white solid, MS: 513, (M−H)⁻.

Example 924-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid

In analogy to example 91, from4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 89) was prepared4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid, yellow foam, MS: 513 (M−H).

Example 933-{4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester

93.1

3-(4-chloromethyl-oxazol-2-yl)-benzoic acid methyl ester was preparedaccording to the procedure by Adam et al. (WO2002083652).

93.2

In analogy to example 75, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and 3-(4-chloromethyl-oxazol-2-yl)-benzoic acid methylester was prepared3-{4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester, yellow foam, MS: 515 (MH⁺).

Example 942-{1-[2-(2,5-diphenyl-oxazol-4-yl)-ethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-{1-[2-(2,5-diphenyl-oxazol-4-yl)-ethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 75) was prepared2-{1-[2-(2,5-diphenyl-oxazol-4-yl)-ethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,off white solid, MS: 545 (MH⁺).

Example 951,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 76) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,orange foam, MS: 511 (MH⁺).

Example 961,1,1,3,3,3-hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 77) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 499 (MH⁺).

Example 971,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol

In analogy to example, 1 from1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 78) was prepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol,light yellow gum, MS: 537 (MH⁺).

Example 981,1,1,3,3,3-hexafluoro-2-{1-[2-(4-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 79) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,light brown foam, MS: 575 (MH⁺).

Example 994-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol

A solution of 80 mg (0.139 mmol) of2-{1-[2-(4-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 98) in 1 mL of methanol was treated with 20 mg Pd/C (10% Pd)and stirred under H₂ at atmospheric pressure for 6 hrs. Filtration andevaporation of the solvent yielded 59 mg (87%) of4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol,light green foam, MS: 485 (MH⁺).

Example 100 dimethyl-carbamic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester

A solution of 25 mg (0.052 mmol)4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol(example 99) in 1 mL of pyridine was treated with 28 mg (0.26 mmol) ofdimethyl carbamoylchloride and stirred at 60° C. for 2 hours. Et₂O andaqueous HCl were added and the phases separated. The aqueous phase wasextracted with Et₂O and the combined organic phases dried over Na₂SO₄.Evaporation of the solvent and column chromatography on silica gel withn-heptane/EtOAc 1:1 yielded 19 mg (66%) of dimethyl-carbamic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester, light yellow solid, MS: 556 (MH⁺).

Example 1011,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-1H-indol-5-yl}-propan-2-ol

In analogy to example 1 from1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-(2-methyl-5-phenyl-oxazol-4-yl)-ethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 85) was prepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 483(MH⁺).

Example 1021,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethyl]-1H-indol-5-yl}-propan-2-ol

In analogy to example 1 from1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 59) was prepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethyl]-1H-indol-5-yl}-propan-2-ol,yellow solid, MS: 535 (M−H)⁻.

Example 1032-{1-[2-ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-{1-[2-ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 82) was prepared2-{1-[2-ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,light yellow solid, MS: 548 (M−H)⁻.

Example 1041,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-1H-indol-5-yl}-propan-2-ol

In analogy to example1,1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 81) was prepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-1H-indol-5-yl}-propan-2-ol,light yellow solid, MS: 534 (M−H)⁻.

Example 105(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester

In analogy to example 1, from(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester (example 83) was prepared(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester, green gum, MS: 557 (MH⁺).

Example 106(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid

In analogy to example 91, from(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester (example 105) was prepared(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid, yellow gum, MS: 543 (MH⁺).

Example 1072-{3-chloro-1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 2, from2-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 12) was prepared2-{3-chloro-1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,off-white solid, MS: 537 (MH⁺), 2Cl.

Example 108 pyrrolidine-1-carboxylic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester

In analogy to example 100, from4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol(example 99) and 1-pyrrolidine-carbonylchloride was preparedpyrrolidine-1-carboxylic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester, light yellow solid, MS: 582 (MH⁺).

Example 109 morpholine-4-carboxylic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester

In analogy to example 100, from4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol(example 99) and morpholine-4-carbonylchloride was preparedmorpholine-4-carboxylic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester, colorless gum, MS: 598 (MH⁺).

Example 1102-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylicacid

In analogy to example 91, from2-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylicacid methyl ester (example 130) was prepared(2-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylicacid, brown solid, MS: 533 (MH⁺), 1Cl.

Example 1112-{1-[2-(2-chloro-phenyl)-5-hydroxymethyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

At 0° C., a solution of 10 mg (0.018 mmol) of2-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylicacid methyl ester (example 130) in 0.3 mL of THF was treated with 1 mg(0.026 mmol) of LiAlH₄ and stirred at RT for 6 hrs. Ice was added andthe mixture distributed between Et₂O and water. Drying of the combinedorganic phases and evaporation yielded 9 mg (95%) of2-{1-[2-(2-chloro-phenyl)-5-hydroxymethyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,off-white solid, MS:518 (MH⁺), 1 Cl.

Example 112N,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide

In analogy to example 1, fromN,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide(example 87) was preparedN,N-dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide,off white solid, MS: 570 (MH⁺).

Example 1132-{1-[2-(3-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol

In analogy to example 1, from2-{1-[2-(3-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 88) was prepared2-{1-[2-(3-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,off white solid, MS: 575 (MH⁺).

Example 1143-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol

In analogy to example 99, from2-{1-[2-(3-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 113) was prepared3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol,light brown solid, MS: 485 (MH⁺).

Example 115 morpholine-4-carboxylic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester

In analogy to example 100, from3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol(example 114) and morpholine-4-carbonylchloride was preparedmorpholine-4-carboxylic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester, light yellow foam, MS: 598 (MH⁺).

Example 116 dimethyl-carbamic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester

In analogy to example 100, from3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol(example 114) and dimethylcarbamoylchloride was prepareddimethyl-carbamic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester, light yellow solid, MS: 556 (MH⁺).

Example 117 pyrrolidine-1-carboxylic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester

In analogy to example 100, from3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol(example 114) and 1-pyrrolidine-carbonylchloride was preparedpyrrolidine-1-carboxylic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester, white solid, MS: 582 (MH⁺).

Example 118(3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester

In analogy to example 83, from3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol(example 114) and methyl bromoacetate was prepared(3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester, off white gum, MS: 557 (MH⁺).

Example 1193-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester

In analogy to example 1, from(3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 90) was prepared3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester, orange solid, MS: 527 (MH⁺).

Example 1204-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester

In analogy to example 1, from(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 89) was prepared4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester, light brown solid, MS: 527 (MH⁺).

Example 1213-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid

In analogy to example 91, from3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 120) was prepared3-{5-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid, brown solid, MS: 513 (MH⁺).

Example 1221,1,1,3,3,3-hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 111, from3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 119) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,yellow oil, MS: 499 (MH⁺).

Example 1234-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid

In analogy to example 91, from4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 119) was prepared4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid, orange solid, MS: 511 (M−H)⁻.

Example 124N,N-dimethyl-3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide

In analogy to example 34, from3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid (example 121) was preparedN,N-dimethyl-3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide,off-white solid, MS: 540 (MH⁺).

Example 125(3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid

In analogy to example 91, from(3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester (example 118) was prepared(3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid, pink solid, MS: 541 (M−H)⁻.

Example 126N,N-dimethyl-4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide

In analogy to example 91, from4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid (example 123) was preparedN,N-dimethyl-4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide,off-white solid, MS: 540 (MH⁺).

Example 1271,1,1,3,3,3-hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 111, from4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 120) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,yellow oil, MS: 499 (MH⁺).

Example 1282-[2,3-dimethyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol

128.1

A solution of 200 mg (0.4 mmol) of2-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 12) in 2 mL of dichloroethane was treated with 0.06 mL (0.8mmol) of DMF and cooled to 0° C. After addition of 0.04 mL (0.44 mmol)of POCl₃ the mixture was allowed to reach RT and stirred for anadditional hour. Distribution of the mixture between Et₂O and H₂O,drying of the combined organic phases over Na₂SO₄ and columnchromatography on silica gel with n-heptane/EtOAc 1:2 yielded 110 mg(52%) of1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indole-3-carbaldehyde,light brown solid, MS: 531 (MH⁺).

128.2

A solution of 50 mg of1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indole-3-carbaldehydein 1 mL of THF was treated at 0° C. with 5 mg (0.14 mmol) of LiAlH₄ andallowed to reach RT within 1 h. Ice cubes were added and the mixturedistributed between Et₂O and H₂O. Drying of the combined organic phasesover Na₂SO₄ and evaporation of the solvent yielded 36 mg of2-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-3-hydroxymethyl-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol,off white solid, 533 (MH⁺).

128.3

A solution of 25 mg of2-{1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-3-hydroxymethyl-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-olin 1 mL of MeOH was treated with Pd/C (10% Pd) and stirred under H₂ atatmospheric pressure for 8 hrs. Filtration and evaporation of thesolvent yielded2-[2,3-dimethyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol,light brown solid, 483 (MH⁺).

Example 1291,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol(example 46), was prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol,brown oil, MS: 483 (MH⁺).

Example 1302-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylicacid methyl ester

In analogy to example 1, from2-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazole-5-carboxylicacid methyl ester (example 45), was prepared2-(2-chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylicacid methyl ester, light yellow semisolid, MS: 545 (M−H).

Example 1311,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol(example 44), was prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol,light yellow oil, MS: 469 (MH⁺).

Example 1321,1,1,3,3,3-hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-2,3,-dihydro-1H-indol-5-yl}-propan-2-ol(example 72), was prepared1,1,1,3,3,3-hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-1H-indol-5-yl}-propan-2-ol,red solid, MS: 498 (MH⁺).

Example 1331,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-2-ylmethyl-1H-indol-5-yl)-propan-2-ol

133.1

In analogy to example 51.3, from2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole(example 51.2) and 2-bromomethyl-naphthalene was prepared1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol,red oil, MS: 440 (MH⁺).

133.2

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol,was prepared1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-2-ylmethyl-1H-indol-5-yl)-propan-2-ol,red solid, MS: 438 (MH⁺).

Example 1341,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-1H-indol-5-yl}-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 74), was prepared1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-1H-indol-5-yl}-propan-2-ol,light brown solid, MS: 546 (MH⁺).

Example 135{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-piperidin-1-yl-methanone

In analogy to example 34, from3-{5-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid (example 121) and piperidine was prepared{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-piperidin-1-yl-methanone,colorless solid, MS: 499 (MH⁺).

Example 136 trans1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-styryl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

136.1

trans 4-chloromethyl-5-methyl-2-styryl-oxazole was prepared fromcinnamaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

136.2

In analogy to example 75.2, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and trans 4-chloromethyl-5-methyl-2-styryl-oxazole wasprepared trans1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-styryl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,orange solid, MS: 497 (MH⁺).

Example 1372-[1-(2-benzyl-5-methyl-oxazol-4-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol

137.1

benzyl-4-chloromethyl-5-methyl-oxazole was prepared fromphenylacetaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

137.2

In analogy to example 75.2, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and 2-benzyl-4-chloromethyl-5-methyl-oxazole was prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-styryl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,red oil, MS: 485 (MH⁺).

Example 1381,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

A solution of 30 mg (0.06 mmol) of1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-styryl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol(example 136) in 1 ml of methanol was treated with 15 mg of Pd/C (10%)and stirred under H₂ at atmospheric pressure for 6 hours. Filtration andevaporation of the solvent gave 24 mg (77%) of1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,light yellow oil, MS: 499 (MH⁺).

Example 1394-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenol

A solution of 1.2 g (2.1 mmol) of2-{1-[2-(4-benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol(example 79) in 15 ml of a 2:1-mixture of methanol and tetrahydrofuranwas treated with 400 mg of Pd/C (10% Pd) and stirred vigorously under H₂at atmospheric pressure during 10 hrs. Filtration, evaporation of thesolvent, and chromatography on silica gel with toluene/EtOAc (gradientfrom 9:1 to 1:1) gave 390 mg (39%) of4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenol,light yellow foam, MS: 487 (MH⁺).

Example 1401,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol

In analogy to example 1, from1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol(example 138) was prepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol,light brown solid, MS: 497 (MH⁺).

Example 1411,1,1,3,3,3-hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

A solution of 1.25 g (2.37 mmol) of3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 90) in 15 ml of THF was treated at 0° C. with180 mg (4.73 mmol) of lithium aluminium hydride and allowed to reach RTwithin 3 hrs. Distribution of the crude between a saturated aqueoussolution of NH₄Cl and EtOAc, drying of the combined organic phases overNa₂SO₄ and evaporation of the solvent gave 1.1 g (93%) of1,1,1,3,3,3-hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,off-white foam, MS: 499 (M−H)⁻.

Example 1421,1,1,3,3,3-hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

In analogy to example 141, from4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester (example 89) was prepared1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,light brown solid, MS: 499 (M−H)⁻.

Example 1431,1,1,3,3,3-hexafluoro-2-(1-{2-[4-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol

143.1

A solution of 100 mg (0.2 mmol) of1,1,1,3,3,3-hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-olin 2 ml of toluene was treated with 87 mg (1.0 mmol) of MnO₂ and stirredat 80° C. during 20 hours. Filtration, evaporation of the solvent andchromatography on silica gel with heptane/EtOAc 4:1 gave 50 mg (50%) of4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzaldehyde,pink solid, MS: 497 (MH⁺).

143.2

A solution of 50 mg (0.1 mmol) of4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzaldehydein 1 ml of THF was cooled to 0° C. and treated with 0.13 ml (0.4 mmol)of a 3M methylmagnesium bromide solution in diethylether. The mixturewas stirred and allowed to reach RT within 1 hr. Distribution of thecrude between a saturated aqueous solution of NH₄Cl and EtOAc, drying ofthe combined organic phases over Na₂SO₄, evaporation of the solvent, andchromatography on silica gel with heptane/EtOAc 4:1 gave 44 mg (85%) of1,1,1,3,3,3-hexafluoro-2-(1-{2-[4-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,off-white solid, MS: 513 (MH⁺).

Example 1441,1,1,3,3,3-hexafluoro-2-(1-{2-[3-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol

144.1

In analogy to example 143.1, from1,1,1,3,3,3-hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-olwas prepared3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzaldehyde,pink solid, MS: 497 (MH⁺).

144.2

In analogy to example 143.2, from3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzaldehydewas prepared1,1,1,3,3,3-hexafluoro-2-(1-{2-[3-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,off-white solid, MS: 513 (MH⁺).

Examples 145 and 146

(2R)1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-oland (2S)1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol

Chiral HPLC of 900 mg (1.68 mmol) of racemic1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol(example 56) gave ca. 300 mg (33%) of (2R)1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-oland ca. 300 mg (33%) of (2S)1,1,1,3,3,3-hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,Colorless solids, MS: 539 (MH⁺).

Example 1471,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-pyridin-3-yl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol

147.1

3-(4-chloromethyl-5-methyl-oxazol-2-yl)-pyridine was prepared from3-pyridinecarboxaldehyde in analogy to the procedure by Binggeli et al.(WO200292084).

147.2

In analogy to example 75.2, from1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol(example 51.1) and 3-(4-chloromethyl-5-methyl-oxazol-2-yl)-pyridine wasprepared1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-pyridin-3-yl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,Light brown gum, MS: 472 (MH⁺).

Example 148

A compound of formula (I) can be used in a manner known per se as theactive ingredient for the production of tablets of the followingcomposition:

Per tablet Active ingredient 200 mg Microcrystalline cellulose 155 mgCorn starch  25 mg Talc  25 mg Hydroxypropylmethylcellulose  20 mg 425mg

Example 149

A compound of formula (I) can be used in a manner known per se as theactive ingredient for the production of capsules of the followingcomposition:

Per capsule Active ingredient 100.0 mg Corn starch  20.0 mg Lactose 95.0 mg Talc  4.5 mg Magnesium stearate  0.5 mg 220.0 mg

Example 150

The following tests were carried out in order to determine the activityof the compounds of the present invention. Background information on theperformed assays can be found in: Nichols J S et al. “Development of ascintillation proximity assay for peroxisome proliferator-activatedreceptor gamma ligand binding domain”, Anal Biochem. 1998, 257: 112–119.

Mammalian expression vectors were constructed to express full-lengthhuman LXR alpha and LXR beta. Bacterial expression vectors wereconstructed to produce glutathione-s-transferase (GST) fused to theligand binding domains (LBD) of human LXR alpha (aa 164 to 447) andhuman LXR beta (aa 155 to 460). To accomplish this, the portions of thesequences encoding the LBDs were amplified from full-length clones byPCR and then subcloned into the plasmid vectors. Final clones wereverified by DNA sequence analysis (Willy et al., Genes Dev. 1995,9:1033–45; Song et al., Proc Natl Acad Sci USA.1994, 91:10809–13).

Induction, expression, and purification of GST-LBD fusion proteins wereperformed in E. coli strain BL21 (pLysS) cells by standard methods (Ref:Current Protocols in Molecular Biology, Wiley Press, edited by Ausubelet al).

Radioligand Binding Assay

LXR alpha and LXR beta receptor binding were assayed in bufferconsisting of 50 mM HEPES, pH 7.4, 10 mM NaCl, 5 mM MgCl₂. For each96-well reaction, 500 ng of GST-LXRA-LBD or 700 ng of GST-LXR beta-LBDfusion proteins were bound to 80 μg or 40 μg SPA beads (PharmaciaAmersham) respectively, in a final volume of 50 μl by shaking. Theresulting slurry was incubated for 1 h at RT and centrifuged for 2 minat 1300×g. The supernatant containing unbound protein was removed, andthe semi-dry pellet containing the receptor-coated beads wasre-suspended in 50 μl of buffer. Radioligand (eg. 100,000 dpm of(N-(2,2,2-trifluoroethyl)-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl)-phenyl]-benzenesulfonamide))was added, and the reaction incubated at RT for 1 h in the presence oftest compounds, and then scintillation proximity counting was performed.All binding assays were performed in 96-well plates and the amount ofbound ligand was measured on a Packard TopCount using OptiPlates(Packard). Dose response curves were measured within a range ofconcentration from 10⁻¹⁰ M to 10⁻⁴ M.

Luciferase Transcriptional Reporter Gene Assays

Baby hamster kidney cells (BHK21 ATCC CCL10) were grown in DMEM mediumcontaining 10% FBS at 37° C. in a 95% 02:5% CO₂ atmosphere. Cells wereseeded in 6-well plates at a density of 10⁵ Cells/well and thenbatch-transfected with either the full-length-LXR× or full-length-LXRβexpression plasmids plus a reporter plasmid expressing luceriferaseunder the control of LXR response elements. Transfection wasaccomplished with the Fugene 6 reagent (Roche Molecular Biochemicals)according to the suggested protocol. Six hours following transfection,the cells were harvested by trypsinization and seeded in 96-well platesat a density of 10⁴ cells/well. After 24 hours to allow attachment ofcells, the medium was removed and replaced with 100 μl of phenolred-free medium containing the test substances or control ligands (finalDMSO concentration: 0.1%). Following incubation of the cells for 24hours with substances, 50 μl of the supernatant was discarded and then50 μl of Luciferase Constant-Light Reagent (Roche MolecularBiochemicals) was added to lyse the cells and initiate the luciferasereaction. Luminescence, as a measure of luciferase activity, wasdetected in a Packard TopCount. Transcriptional activation in thepresence of a test substance was expressed as fold-change inluminescence compared to that of cells incubated in the absence of thesubstance. EC₅₀ values were calculated using the XLfit program (IDBusiness Solutions Ltd. UK).

The compounds according to formula (I) have an activity in at least oneof the above assays (EC50 or IC50) of 0.1 nM to 100 uM, preferably 0.1nM to 1 uM. (uM means micromolar).

For example, the following compounds showed the following IC50 values inthe binding assay:

LXRalpha LXRbeta Binding Binding IC50 IC50 Example [umol/l] [umol/l] 500.02 0.006 80 0.03 0.05

These results were obtained by using the foregoing test.

It is to be understood that the invention is not limited to theparticular embodiments of the invention described above, as variationsof the particular embodiments may be made and still fall within thescope of the appended claims.

1. A compound of formula (I):

wherein: R¹ is hydrogen, alkyl, halogen, formyl, hydroxyalkyl ortrifluoromethyl; R² is hydrogen, alkyl, alkenyl, alkynyl, cyano orhalogen; R³ is hydrogen or alkyl; R⁴ is hydrogen, alkyl, hydroxy oralkoxy; R⁵ and R⁶ are independently selected from hydrogen, alkyl,arylalkyl, heteroarylalkyl, hydroxyalkyl, alkoxycarbonyl, aryl andheteroaryl; A is aryl or heterocyclyl, wherein aryl and heterocyclyl areoptionally substituted with one to three substituents independentlyselected from alkyl, halogen, amino, hydroxyalkyl, aryl, aryloxy,alkoxy, arylalkyl, arylalkenyl, alkoxycarbonylamino, aminocarbonyloxy,carboxy, alkoxycarbonyl, alkoxycarbonylalkyl, aminoalkyl,trifluoromethyl, arylalkylaminocarbonyl,alkoxycarbonylalkylaminocarbonyl, indolylalkylaminocarbonyl,morpholinylcarbonyl, aminocarbonyl, aminocarbonylalkyl,aminocarbonylalkoxy, alkoxycarbonylalkoxy, pyridinylalkylaminocarbonyl,alkyloxycarbonylalkylaryl, alkyloxycarbonylalkoxyaryl, carboxyalkylaryl,carboxyalkoxyaryl, aminocarbonylalkylaryl, aminocarbonylalkoxyaryl,aminocarbonylamino, aminocarbonyloxy, aminocarbonyloxyaryl,carboxyalkyl, carboxyalkoxy, cycloalkylaminocarbonyl,morpholinylcarbonyloxyaryl, morpholinylcarbonylaryl, arylalkoxyaryl,aminocarbonylaryl, pyrrolidinylcarbonyloxyaryl,pyrrolidinylcarbonylaryl, piperidinylcarbonylaryl,piperidinylcarbonyloxyaryl; hydroxyalkylaryl, hydroxy(carboxy)alkylaryl,hydroxy(alkoxycarbonyl)alkylaryl, hydroxy(aminocarbonyl)alkylaryl andpyridinyl; m is zero, 1, 2 or 3; n is zero or 1; p is zero, 1, 2 or 3;with the proviso that the sum of m, n and p is 1, 2, 3 or 4; and,wherein the compound is not2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;and, wherein the bond between the carbon atoms C^(a) and C^(b) is acarbon carbon single or double bond and in case the bond between C^(a)and C^(b) is a carbon carbon double bond R³ and R⁴ are absent; andpharmaceutically acceptable salts and pharmaceutically acceptable estersthereof.
 2. The compound according to claim 1, wherein R¹ is hydrogen,alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl; R² is hydrogen,alkyl, alkenyl, alkynyl, cyano or halogen; R³ is hydrogen or alkyl; R⁴is hydrogen, alkyl, hydroxy or alkoxy; R⁵ and R⁶ are independentlyselected from hydrogen, alkyl, arylalkyl, heteroarylalkyl, hydroxyalkyl,alkoxycarbonyl, aryl and heteroaryl; A is aryl or heterocyclyl, whereinaryl and heterocyclyl are optionally substituted with one to threesubstituents independently selected from alkyl, halogen, amino,hydroxyalkyl, aryl, aryloxy, alkoxy, arylalkyl, alkoxycarbonylamino,aminocarbonyloxy, carboxy, alkoxycarbonyl, alkoxycarbonylalkyl,aminoalkyl, trifluoromethyl, arylalkylaminocarbonyl,alkoxycarbonylalkylaminocarbonyl, indolylalkylaminocarbonyl,morpholinylcarbonyl, aminocarbonyl, aminocarbonylalkyl,aminocarbonylalkoxy, alkoxycarbonylalkoxy, pyridinylalkylaminocarbonyl,alkyloxycarbonylalkylaryl, alkyloxycarbonylalkoxyaryl, carboxyalkylaryl,carboxyalkoxyaryl, aminocarbonylalkylaryl, aminocarbonylalkoxyaryl,aminocarbonylamino, aminocarbonyloxy, aminocarbonyloxyaryl,carboxyalkyl, carboxyalkoxy, cycloalkylaminocarbonyl,morpholinylcarbonyloxyaryl, morpholinylcarbonylaryl, arylalkoxyaryl,aminocarbonylaryl, pyrrolidinylcarbonyloxyaryl,pyrrolidinylcarbonylaryl, piperidinylcarbonylaryl,piperidinylcarbonyloxyaryl; hydroxyalkylaryl, hydroxy(carboxy)alkylaryl,hydroxy(alkoxycarbonyl)alkylaryl, hydroxy(aminocarbonyl)alkylaryl andpyridinyl; m is zero, 1, 2 or 3; n is zero or 1; p is zero, 1, 2 or 3;with the proviso that the sum of m, n and p is 1, 2, 3 or 4; and,wherein the compound is not2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;and, wherein the bond between the carbon atoms C^(a) and C^(b) is acarbon carbon single or double bond and in case the bond between C^(a)and C^(b) is a carbon carbon double bond R³ and R⁴ are absent; andpharmaceutically acceptable salts and pharmaceutically acceptable estersthereof.
 3. The compound according to claim 1, wherein R¹ is methyl. 4.The compound according to claim 1, wherein R² is hydrogen, alkyl orhalogen.
 5. The compound according to claim 4, wherein R² is hydrogen.6. The compound according to claim 1, wherein R³ is hydrogen.
 7. Thecompound according to claim 1, wherein R⁴ is hydrogen.
 8. The compoundaccording to claim 1, wherein one of R⁵ and R⁶ is hydrogen and the otherone is hydroxyalkyl or aryl.
 9. The compound according to claim 1,wherein m is zero or
 1. 10. The compound according to claim 1, wherein nis zero.
 11. The compound according to claim 1, wherein p is zero or 1.12. The compound according to claim 1, wherein m is 1, n is zero and pis zero.
 13. The compound according to claim 1, wherein the bond betweenthe carbon atoms C^(a) and C^(b) is a carbon carbon single bond.
 14. Thecompound according to claim 1, wherein the bond between the carbon atomsC^(a) and C^(b) is a carbon carbon double bond and R³ and R⁴ are absent.15. The compound according to claim 1, wherein A is phenyl, oxazolyl,quinolinyl, thiazolyl, naphthalenyl, benzothiophenyl, isoxazolyl,quinolinyl, pyridinyl, 2H-pyrazol-3-yl or isooxazolyl, wherein phenyl,oxazolyl, quinolinyl, thiazolyl, naphthalenyl, benzothiophenyl,isoxazolyl, quinolinyl, pyridinyl, 2H-pyrazol-3-yl and isooxazolyl areoptionally substituted with one to three substituents independentlyselected from the group consisting of alkyl, halogen, amino,hydroxyalkyl, aryl, aryloxy, alkoxy, arylalkyl, alkoxycarbonylamino,aminocarbonyloxy, carboxy, alkoxycarbonyl, alkoxycarbonylalkyl,aminoalkyl, trifluoromethyl, arylalkylaminocarbonyl,alkoxycarbonylalkylaminocarbonyl, indolylalkylaminocarbonyl,morpholinylcarbonyl, aminocarbonyl, aminocarbonylalkyl,aminocarbonylalkoxy, alkoxycarbonylalkoxy, pyridinylalkylaminocarbonyl,alkyloxycarbonylalkylaryl, alkyloxycarbonylalkoxyaryl, carboxyalkylaryl,carboxyalkoxyaryl, aminocarbonylalkylaryl, aminocarbonylalkoxyaryl,aminocarbonylamino, aminocarbonyloxy, aminocarbonyloxyaryl,carboxyalkyl, carboxyalkoxy, cycloalkylaminocarbonyl,morpholinylcarbonyloxyaryl, morpholinylcarbonylaryl, arylalkoxyaryl,aminocarbonylaryl, pyrrolidinylcarbonyloxyaryl,pyrrolidinylcarbonylaryl, piperidinylcarbonylaryl andpiperidinylcarbonyloxyaryl.
 16. The compound according to claim 1,wherein A is phenyl, oxazol-2-yl or oxazol-4-yl, wherein phenyl,oxazol-2-yl and oxazol-4-yl are optionally substituted with one to threesubstituents independently selected from alkyl, tolyl, ethyl-phenyl,trifluoromethyl-phenyl, fluoro-phenyl, chloro-phenyl,carboxymethoxy-phenyl, aminocarbonylmethoxy-phenyl, carboxy-phenyl,hydroxyl-phenyl, hydroxymethyl-phenyl and aminocarbonyl-phenyl.
 17. Thecompound according to claim 1, wherein A is phenyl.
 18. The compoundaccording to claim 1, wherein A is oxazolyl which is substituted with afirst substituent which is alkyl and a second substituent which isphenyl or pyridinyl, which phenyl is substituted with hydroxyalkyl. 19.The compound according to claim 18, wherein A is2-[4-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl,2-[3-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl or5-methyl-2-pyridin-3-yl-oxazol-4-ylmethyl.
 20. The compound according toclaim 1 selected from the group consisting of:1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;2-(1-Benzyl-3-chloro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-{1-[2-(4-Ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol;2-(1-Benzyl-3-fluoro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(3-morpholin-4-ylmethyl-benzyl)-1H-indol-5-yl]-propan-2-ol;3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid methyl ester;2-[1-(3-Dimethylaminomethyl-benzyl)-2-methyl-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-1H-indol-5-yl]-propan-2-ol;2-{1-[2-(3-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-{1-[2-(4-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-1H-indol-5-yl)-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol;2-(1-Benzyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-phenethyl-1H-indol-5-yl)-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;2-(1-Benzyl-2,3-dichloro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-{1-[2-(4-tert-Butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-{1-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-(1-Benzyl-2,3-diiodo-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;1-Benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indole-2-carbaldehyde;2-(1-Biphenyl-3-ylmethyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-1H-indol-5-yl)-propan-2-ol;2-(1-Benzyl-3-iodo-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;N-Benzyl-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide;4-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid methyl ester;N-Methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-phenethyl-benzamide;(Methyl-{3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoyl}-amino)-aceticacid ethyl ester;3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzoicacid;N-[2-(1H-Indol-3-yl)-ethyl]-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide;{3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-morpholin-4-yl-methanone;N,N-Dimethyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide;N-Methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-(2-pyridin-2-yl-ethyl)-benzamide;N-Methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-N-pyridin-2-ylmethyl-benzamide;2-[1-Benzyl-2-(1-hydroxy-ethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol;1-[1-Benzyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indol-2-yl]-propan-1-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[1-(2-hydroxy-1-phenyl-ethyl)-2-methyl-1H-indol-5-yl]-propan-2-ol;2-(1-Benzyl-2-hydroxymethyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;N-Cyclohexyl-N-methyl-3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-benzamide;2-[1-(5-Chloro-benzo[b]thiophen-3-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;2-(2-Chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazole-5-carboxylic-acidmethyl ester;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;2-(1-Benzyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-{1-[2-(4-Ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[1-(3-hydroxymethyl-benzyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;2-{1-[2-(3-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(2-trifluoromethyl-quinolin-6-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-naphthalen-1-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-phenyl-aceticacid methyl ester;2-{1-[2-(4-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-quinolin-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;2-(1-Biphenyl-3-ylmethyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[4-(4-trifluoromethyl-phenoxy)-benzyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;2-{1-[2-(4-tert-Butyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-(1-Benzhydryl-2-methyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid;4-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoicacid methyl ester;1,1,1,3,3,3-Hexafluoro-2-[-(2-hydroxy-1-phenyl-ethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;2-{1-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;2-{1-[2-(2,5-Diphenyl-oxazol-4-yl)-ethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;2-{1-[2-(4-Benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-(1-Benzyl-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;2-{1-[2-Ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;(4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester;(4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-(2-methyl-5-phenyl-oxazol-4-yl)-ethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;N,N-Dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide;2-{1-[2-(3-Benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester;3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester;3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid;4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid;3-{4-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester;2-{1-[2-(2,5-Diphenyl-oxazol-4-yl)-ethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(2-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol;2-{1-[2-(4-Benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol;Dimethyl-carbamic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl]-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-ylmethyl]-1H-indol-5-yl}-propan-2-ol;2-{1-[2-Ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-methyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethyl]-1H-indol-5-yl}-propan-2-ol;(4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester;(4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid;2-{3-Chloro-1-[2-(3-chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;Pyrrolidine-1-carboxylic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester; Morpholine-4-carboxylic acid4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester;2-(2-Chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylicacid;2-{1-[2-(2-Chloro-phenyl)-5-hydroxymethyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;N,N-Dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide;2-{1-[2-(3-Benzyloxy-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol;Morpholine-4-carboxylic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester; Dimethyl-carbamic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester; Pyrrolidine-1-carboxylic acid3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenylester;(3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid methyl ester;3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester;4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid methyl ester;3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid;N,N-Dimethyl-3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide;(3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid;N,N-Dimethyl-4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;2-[2,3-Dimethyl-1-(5-methyl-2-phenyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-o-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;2-(2-Chloro-phenyl)-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazole-5-carboxylicacid methyl ester;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[3-(4-fluoro-phenoxy)-benzyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-naphthalen-2-ylmethyl-1H-indol-5-yl)-propan-2-ol;1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-naphthalen-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethyl]-1H-indol-5-yl}-propan-2-ol;and{3-[2-Methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-phenyl}-piperidin-1-yl-methanone.21. The compound according to claim 1 selected from the group consistingof:1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol;2-(1-Benzyl-3-chloro-2-methyl-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-1H-indol-5-yl}-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(2-fluoro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;2-{1-[2-(3-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-phenethyl-1H-indol-5-yl)-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-m-tolyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol;2-{1-[2-(4-Ethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;2-{1-[2-(3-Chloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol;1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol;(4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid;N,N-Dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide;3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid;4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid;4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenol;(4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid;N,N-Dimethyl-2-(4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-acetamide;3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl)-phenol;3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid;1,1,1,3,3,3-Hexafluoro-2-{1-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol;4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzoicacid;N,N-Dimethyl-3-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide;(3-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-phenoxy)-aceticacid;N,N-Dimethyl-4-{5-methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-indol-1-ylmethyl]-oxazol-2-yl}-benzamide;and1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-1H-indol-5-yl}-propan-2-ol.22. The compound according to claim 1 selected from the group consistingof: Trans1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-styryl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,2-[1-(2-Benzyl-5-methyl-oxazol-4-ylmethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol,1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,4-{5-Methyl-4-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-oxazol-2-yl}-phenol,1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-phenethyl-oxazol-4-ylmethyl)-1H-indol-5-yl]-propan-2-ol,1,1,1,3,3,3-Hexafluoro-2-{11-[2-(3-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,1,1,1,3,3,3-Hexafluoro-2-{1-[2-(4-hydroxymethyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,1,1,1,3,3,3-Hexafluoro-2-(1-12-[4-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,1,1,1,3,3,3-Hexafluoro-2-(1-{2-[3-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,(2R)1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,(2S)1,1,1,3,3,3-Hexafluoro-2-{2-methyl-1-[5-methyl-2-(3-trifluoromethyl-phenyl)-oxazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-propan-2-ol,and1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-pyridin-3-yl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,and pharmaceutically acceptable salts and pharmaceutically cceptableesters thereof.
 23. The compound according to claim 1 selected from thegroup consisting of:1,1,1,3,3,3-Hexafluoro-2-(1-{2-[4-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,1,1,1,3,3,3-Hexafluoro-2-(1-{2-[3-(1-hydroxy-ethyl)-phenyl]-5-methyl-oxazol-4-ylmethyl}-2-methyl-1H-indol-5-yl)-propan-2-ol,and1,1,1,3,3,3-Hexafluoro-2-[2-methyl-1-(5-methyl-2-pyridin-3-yl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol,and pharmaceutically acceptable salts and pharmaceutically cceptableesters thereof.
 24. A process for the preparation of compounds offormula (I) according to claim 1, comprising one of the followingreactions: a) reaction of a compound according to formula (II):

in the presence of a compound according to formula (III):

wherein R¹ to R⁶, A, m, n and p are defined as in claim 1 and LG is aleaving group and, wherein hydroxy groups are optionally protected; b)oxidation of a compound according to formula (Ia):

wherein R¹, R², R⁵, R⁶, A, m, n and p are defined as in claim 1, R³ andR⁴ are hydrogen and, wherein hydroxy groups are optionally protected.25. A pharmaceutical composition comprising a therapeutically effectiveamount of a compound of formula (I):

wherein: R¹ is hydrogen, alkyl, halogen, formyl, hydroxyalkyl ortrifluoromethyl; R² is hydrogen, alkyl, alkenyl, alkynyl, cyano orhalogen; R³ is hydrogen or alkyl; R⁴ is hydrogen, alkyl, hydroxy oralkoxy; R⁵ and R⁶ are independently selected from hydrogen, alkyl,arylalkyl, heteroarylalkyl, hydroxyalkyl, alkoxycarbonyl, aryl andheteroaryl; A is aryl or heterocyclyl, wherein aryl and heterocyclyl areoptionally substituted with one to three substituents independentlyselected from alkyl, halogen, amino, hydroxyalkyl, aryl, aryloxy,alkoxy, arylalkyl, arylalkenyl, alkoxycarbonylamino, aminocarbonyloxy,carboxy, alkoxycarbonyl, alkoxycarbonylalkyl, aminoalkyl,trifluoromethyl, arylalkylaminocarbonyl,alkoxycarbonylalkylaminocarbonyl, indolylalkylaminocarbonyl,morpholinylcarbonyl, aminocarbonyl, aminocarbonylalkyl,aminocarbonylalkoxy, alkoxycarbonylalkoxy, pyridinylalkylaminocarbonyl,alkyloxycarbonylalkylaryl, alkyloxycarbonylalkoxyaryl, carboxyalkylaryl,carboxyalkoxyaryl, aminocarbonylalkylaryl, aminocarbonylalkoxyaryl,aminocarbonylamino, aminocarbonyloxy, aminocarbonyloxyaryl,carboxyalkyl, carboxyalkoxy, cycloalkylaminocarbonyl,morpholinylcarbonyloxyaryl, morpholinylcarbonylaryl, arylalkoxyaryl,aminocarbonylaryl, pyrrolidinylcarbonyloxyaryl,pyrrolidinylcarbonylaryl, piperidinylcarbonylaryl,piperidinylcarbonyloxyaryl; hydroxyalkylaryl, hydroxy(carboxy)alkylaryl,hydroxy(alkoxycarbonyl)alkylaryl, hydroxy(aminocarbonyl)alkylaryl andpyridinyl; m is zero, 1, 2 or 3; n is zero or 1; p is zero, 1, 2 or 3;with the proviso that the sum of m, n and p is 1, 2, 3 or 4; and,wherein the compound is not2-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-1,1,1,3,3,3-hexafluoro-propan-2-ol;and, wherein the bond between the carbon atoms C^(a) and C^(b) is acarbon carbon single or double bond and in case the bond between C^(a)and C^(b) is a carbon carbon double bond R³ and R⁴ are absent; andpharmaceutically acceptable salts and pharmaceutically acceptable estersthereof and a pharmaceutically acceptable carrier.